The Panacea Vol 2 2023

THE PANACEA EPITOME OF VOL.2 | 2023

Contents Editorial Board ................................................................................................................................................................................2 Foreword ...........................................................................................................................................................................................3 Dean’s Faculty of Pharmacy .....................................................................................................................................................3 Editor-in-Chief.........................................................................................................................................................................4 Editorial Notes.........................................................................................................................................................................5 Research Highlights..........................................................................................................................................................................8 A glance at Malaysia COVID-19 themed innovations..................................................................................................................8 The Pharmaceutical Technology Landscape: Present and Developing Trends .........................................................................9 Formulation and Characterisation of Juglone-Loaded Poloxamer-Based Hydrogels or Diabetic Wounds ...............................10 Microneedle For Drug Delivery ................................................................................................................................................ 11 Nose-to-brain drug delivery: Challenges and future prospects towards brain targeting therapy.............................................14 Anti-microbial sutures: an overview .......................................................................................................................................15 Centella asiatica: A Current Trend In Cosmetics With Therapeutic Potential ..........................................................................16 Virtual Screening of Potential Drug-Like Inhibitors against SARS-COV-2 NSP12 RNA-Dependent RNA Polymerase ................17 Ergothioneine: “Longevity Vitamin” From Farm to Fork...........................................................................................................18 Defueling cancer: Lipid metabolism as an emerging therapeutic target for gynaecological cancers ......................................19 Exploring the role of the cholesterogenic gene, FDFT1 in obesity ...........................................................................................21 Online learning and public health at higher education institutions in low- and middle-income countries: a catalyst or turn-off? ............................................................................................................................................................22 Postgraduate Society .....................................................................................................................................................................25 Editorial Board Advisor Prof. Dr. Hasniza Zaman Huri Assoc. Prof. Dr. Najihah Mohd Hashim Prof. Dr. Chung Lip Yong Editor-in-Chief Assoc. Prof. Dr. Rozana Othman Editor Coordinator Dr. Syed Mahmood Editor Dr. Zarif Mohamed Sofian Dr. Phan Chia Wei Dr. Fatiha Hana Shabaruddin Committee Dr. Chanthiriga Ramasindarum Syamira Azwin Safarudin 2 / THE PANACEA / VOLUME 2 2023

Foreword from the Dean’s Faculty of Pharmacy Welcome to the second edition of The Panacea, our Faculty of Pharmacy bulletin. We have celebrated many milestones since we started operating as the newest Faculty in Universiti Malaya in 2019. Our journey started as the Department of Pharmacy, established as a department under the Faculty of Medicine back in 1995. This faculty was fully operational in September 2019, with the appointment of the dean and our two deputy deans on 1st September 2019. While our faculty status is recent, we bring over two decades of achievements and experience from our existence as the Department of Pharmacy. Since our beginnings as the Department of Pharmacy, there have been more than 20 batches of students who have graduated from our Bachelor of Pharmacy (Honours) degree program, which has produced more than 1300 pharmacists and hundreds of students pursued their postgraduate degrees with us. In addition, from 2023 faculty of pharmacy is also offering two new master program (course work) in pharmaceutical technology and chemistry departments. Over the years, we have charted a journey that centered on excellence, progress, and growth, culminating in the current achievement of our ranking to date at # 101- 150 by the QS Global World Ranking for Pharmacology and Pharmacy. As we move forward, we hope to continue our tradition of excellence and positively impact the community around us. Recently, the Faculty of Pharmacy, Universiti Malaya is honoured to be one of the founding members of the Global Alliance of Development of Pharmaceutical Science (GADPSU), a partnership established among the school of pharmacy or pharmaceutical sciences worldwide initiated by China Pharmaceutical University (CPU). Global Alliance for the Development of Pharmacy Schools and Universities is a global educational association voluntarily formed by pharmaceutical schools and universities that share a common vision and strategic goals in the field of pharmacy and health. GADPSU is committed to establishing a global exchange and cooperation platform for education, science and technology and talent cultivation in the field of pharmacy and health among its members, promoting closer partnerships among member schools and universities, non-profit government organizations and the industry, advancing the sustainable development of global pharmaceutical schools and universities, driving the trend of the biotechnology revolution, and contributing to human health and well-being. Lastly, my heartiest congratulations to the editorial committee of The Panacea and thank you for the hard work in making this bulletin a reality. This inaugural edition of The Panacea reflects the aspirations of the faculty to contribute to the betterment of society. We hope that our bulletin will benefit our professional colleagues as well as the wider society. Warm wishes L Prof. Dr. Hasniza Zaman Huri Dean Faculty of Pharmacy Universiti Malaya THE PANACEA / VOLUME 2 2023 / 3

Foreword from the Editor-in-Chief We are delighted to present the second issue of The Panacea, where knowledge meets innovation, and ideas take flight. In this issue, we delve into the forefront of cutting-edge research, shedding light on groundbreaking discoveries and emerging trends in various research fields. It is our wish to foster vibrant exchange of ideas and to facilitate the dissemination of knowledge within our academic and research community, and to the public. With every issue, we aim to inspire, inform and ignite your curiosity. The Panacea is a platform for all of us to connect, collaborate and contribute to the advancement of knowledge. We invite you to explore the diverse world of research showcased in this edition. Thank you for your support. Together we can push the boundaries of knowledge and continue to inspire many blooming researchers L Assoc. Prof. ChM. Dr. Rozana Othman Editor-in-Chief The Panacea 4 / THE PANACEA / VOLUME 2 2023

Editorial Notes The Panacea editorial office would to thank our outstanding scientific contributions, which would not be possible without our authors, reviewers and Editorial Board Members. The Panacea provides an advance update in research and development in the pharmaceutical research. Panacea aim to serves as the outlet for internationally relevant pharmaceutical research through. Pharmaceutical development worldwide is remarkable and reaches every individual across the globe. The effort made by pharmaceutical industries, academia, and social pharmacy practitioners (hospital and community pharmacist) results in consistently high-quality products and information, thus improving the quality of life. To maintain and improve these standards, many institutes such as USFDA, NPRA, and WHO, provide updated knowledge on various issues related to pharmaceutical drugs and their use. Academia plays a significant role in enlightening the industry and making this knowledge a reality on the ground. Panacea’s mission is to provide a platform and avenue for academia to publish their research updates and ideas and disseminate innovative thoughts on pharmaceutical, life sciences, and healthcare-related issues. Research papers give a genuine insight into specific areas by using real-world examples to report significant developments, describing the relevant theoretical background with a workable algorithm. It covers a multi-disciplinary scope covering “Pharmacy & Pharmacology, Precision Medicine and Natural Products” being the true home for pharmaceutical scientists. It has special sections on pharmaceutical technology, pharmaceutical chemistry, life sciences and pharmacy practice. Panacea is the first magazine from the Faculty of Pharmacy that aims to publish industry updates and activities throughout the year. The second issue covers 2022 activities. The information will be categorised as follows: • Research papers • Review articles • Abstracts • Expert opinions, and • Social and educational activities. The Faculty of Pharmacy hopes this initiative will give readers a better understanding of what is happening in the industry and enhance the quality of learning. We welcome enquiries and feedback on this issue and potential publications in future issues L Dr. Syed Mahmood Editorial Coordinator The Panacea THE PANACEA / VOLUME 2 2023 / 5

VVIISSIIOONN VISION MMMIIISSSSSSIIIOOONNN To be a globally eminent faculty in pharmacy education, research and innovation To produce high-quality graduates and research towards enhancement of global health and well-being 6 / THE PANACEA / VOLUME 2 2023

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A glance at Malaysia COVID-19 themed innovations Wong Tin Wui1,2* 1 Non-Destructive Biomedical and Pharmaceutical Research Centre, Smart Manufacturing Research Institute, Universiti Teknologi MARA Selangor, 42300, Puncak Alam, Selangor, Malaysia. 2 Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA Selangor, 42300, Puncak Alam, Selangor, Malaysia. *[email protected] permutations can be wrangled with ease. The respective administrative data sets cover comprehensively (1) COVID-19 confirmed cases, (2) clinically audited deaths due to COVID-19, (3) intensive care unit admission with COVID-19, (4) all supervised and approved COVID-19 tests conducted in screening facilities, (5) COVID-19 vaccination records, and (6) output of check-in-based automated contact tracing. The innovation enables high-speed and rigorous data research throughout the vaccination drive. The research output provides evidence-based decisions/policies being made timely by Ministries. Automated recognition system for percentage score of lung coronavirus The lung COVID-19, automated recognition system developed by the Faculty of Electrical Engineering Technology, Universiti Malaysia Perlis,Malaysia(https:// mte.org.my/automated-recognitionsystem-for-percentage-score-of-lungcoronavirus-disease-2019-covid-19- involvement/). Earlier, the healthcare professionals adopted the computerized tomography scans to diagnose patients’ lungs. Nonetheless, it is challenging to compute the viral load in the lungs. As such, an automatic recognition system based on image processing technology is developed. Surveillance methods and feature extraction are used to detect viruses. The automated recognition is mediated over computerized tomography scan images through an image recognition system in MATLAB R2021b software. The technology will detect the amount of virus in a patient’s lungs digitally. The viral load score is divided into three categories, namely mild (25 % or less), moderate (26-75 %), and severe (> 75 %). ChatWithMe The World Health Organization (WHO) has declared COVID-19 as a public health emergency at a global scale. In an effort to curb the COVID-19 outbreak, Malaysia has taken unprecedented steps, prohibiting movement and mass gatherings nationwide. While these steps are critical to controlling the spread of COVID-19, they negatively impact mental health, both short- and long-term. The public may experience psychological issues, including stress, anxiety, and fear. The strict stay-at-home orders and physical Introduction The COVID-19 pandemic is marked by a widespread Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the development of serious medical complications such as acute respiratory distress syndrome and death. Together with lockdown and safety measures implemented to curb the virus spread, the SARS-CoV-2 infection significantly impacts lives and livelihoods, which warrants the advancement of innovations in therapeutics, sensor engineering, education system, information technology, management, and practice. Malaysia is adopting the National Investment Aspirations, a forward-looking national policy aimed at attracting suitable investments, building innovation capacity, and increasing both productivity and economic growth in the post-pandemic future (Outlook and Policy in 2021, 2022). Through national and international collaborative efforts, Malaysian scientists have developed numerous innovations to improve the quality of life. The following highlights showcase the recent development in data practice, medical diagnosis and analysis, and mental health counselling in response to the challenges incurred by the COVID-19 pandemic (Malaysia Technology Expo, 2022). Innovation in data practices for COVID-19 vaccine effectiveness research The data practice innovation is developed by the Institute for Clinical Research, National Institutes of Health, Ministry of Health Malaysia (https://mte.org.my/ innovation-in-data-practices-for-covid19-vaccine-effectiveness-research-therecovam-study-group/). It is aimed to aid the dissemination of time-critical national policy on COVID-19 vaccination programme and epidemic management. The data practice innovation evaluates the effectiveness of the diverse range of COVID-19 vaccines administered in Malaysia through an electronic system developed that (1) ensures timely access to and consistency in multiple discrete platforms of purpose-built administrative data sets, (2) consolidates various data sets to reach a ‘complete’ picture of the COVID-19 epidemic and vaccine rollout at the individual-level, and (3) introduces flexibility in data consolidation environment for maximal ‘branch-ability’ where project-specific distancing have resulted in behavioural changes, shutting down normal day-today functions. Suicide is a common risk for individuals with mental illness. In Malaysia, a rise in suicides amid COVID-19 pandemic is apparent. Averagely, suicide cases doubled in the first five months in 2021 (94 patients a month) compared to 2019 (51 cases a month). WHO recommends a psychiatrist-to-resident ratio at 1 to 10,000. Unfortunately, in Malaysia, the ratio is 1 to 200,000. The lack of access to mental health services may lead to a higher incidence of mental health issues and increased suicide statistics. The current intervention has mental health professionals screen individuals for suicide risk. Some individuals may attempt to conceal their suicidal tendency. On this note, ‘ChatWithMe’, an artificial intelligence chatbot that uses deep learning and natural language processing to detect user’s emotions and identify individuals at risk of suicide based on a written text conversation, is innovated by Multimedia University, Malaysia (https:// mte.org.my/chatwithme/). ChatWithMe uses contextual and keyword recognition-based methods to learn and understand the context of the input texts. It combines a Bidirectional Encoder Representation from Transformer (BERT) with zero-shot learning in a two-stage classification chatbot system. The first stage is to determine whether individuals, through their conversations with the chatbot have suicidal ideation. The output of this stage will then be channeled as input to the second stage. In the second stage, zero-shot learning is applied for intent classification. ChatWithMe can initiate conversation, provide an appropriate response based on the user’s input, and direct them to mental health professionals when necessary. ChatWithMe spots people with suicidal ideation through text conversations with the user. The innovation opens a new possibility for suicide preventive intervention. Reference 1. Malaysia Tech. Expo, 2022. https://mte.org. my/mte-2022-covid-19-intl-innovationawards-results/ 2. Outlook and Policy on 2021. Innovation Malaysia: Towards higher quality growth in a post-pandemic future. Economic and Monetary Review 2020, 77-89. https://www. bnm.gov.my/documents/20124/3026377/ emr2020_en_box2_innovation.pdf L 8 / THE PANACEA / VOLUME 2 2023 RESEARCH HIGHLIGHTS

The Pharmaceutical Technology Landscape: Present and Developing Trends Saeid Mezail Mawazi*, Syed Mahmood, Riyanto Teguh Widodo 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia. Corresponding author* [email protected] Pharmaceutical Technology is the science and technology utilised in discovering, manufacturing, and distributing pharmaceutical medications. This involves researching medication delivery techniques, drug formulation, and pharmaceutical production procedures. Pharmaceutical technology strives to provide safe and effective pharmaceuticals that can be administered to patients most efficiently and conveniently. It entails developing and improving medication formulations and delivery mechanisms using diverse technologies and techniques such as nanotechnology, biotechnology, and pharmacology 1. Pharmaceutical technology also includes the investigation of medication stability and shelf life, drug safety, and regulatory criteria for drug approval and commercialisation. It is crucial to ensure that pharmaceuticals are safe, efficacious, and easily available to patients. Pharmaceutical technology has advanced significantly in recent years. These advancements have aided in the discovery and manufacture of novel pharmaceuticals, the improvement of drug delivery systems, and the improvement of patient outcomes. We will explore the most critical pharmaceutical technology issues affecting the future of medicine in this article 2. Advanced Drug Delivery Systems In recent years, there has been a growing emphasis on creating enhanced drug delivery methods that may increase therapeutic effectiveness and safety. Nanotechnology-based drug delivery systems, implantable drug delivery systems, and tailored drug delivery systems are among the most promising innovations in this sector 3. Machine Learning in Drug Discovery Artificial intelligence (AI) use in drug development is a young and fast-expanding topic. Artificial intelligence-based technologies may assist researchers in identifying novel therapeutic targets, predicting treatment effectiveness, and shortening drug development schedules. Machine learning, deep learning, and natural language processing are some of the most promising AI-based technologies in this discipline 4. Personalised Medicine Customised medicine is a notion gaining traction in the pharmaceutical business. It entails adapting medical therapy to a patient’s unique traits, such as genetic composition, lifestyle, and medical history. This method can potentially enhance treatment results, decrease side effects, and boost patient satisfaction 5. 3-D printing in the Pharmaceutical Industry 3-D printing has emerged as a disruptive technique in various areas, including medicine. Printing medicine formulations, medical gadgets, and even organs for donation are possible using this technique. 3D printing may potentially aid in shortening medication development schedules and allow small-batch drug manufacture 6. Pharmaceutical technology is quickly evolving, and new discoveries will likely change how pharmaceuticals are identified, created, and supplied to patients. The technologies addressed in this article are among the most crucial subjects determining pharmaceutical technology’s future. Ultimately, advances in drug delivery technologies, artificial intelligence, customised medicine, and 3D printing are projected to influence the Pharmaceutical Technology Future pharmaceutical industry substantially. References 3. Tierney R, Hermina W, Walsh S. The pharmaceutical technology landscape: A new form of technology roadmapping. Technol Forecast Soc Change. 2013;80(2):194-211. 4. Swarbrick J. Encyclopedia of Pharmaceutical Technology: Volume 6. CRC press; 2013. 5. Shekunov BY, York P. Crystallization processes in pharmaceutical technology and drug delivery design. J Cryst Growth. 2000;211(1-4):122-136. 6. Vamathevan J, Clark D, Czodrowski P, et al. Applications of machine learning in drug discovery and development. Nat Rev Drug Discov. 2019;18(6):463-477. 7. Vizirianakis IS. Pharmaceutical education in the wake of genomic technologies for drug development and personalised medicine. Eur J Pharm Sci. 2002;15(3):243-250. 8. Mohammed AA, Algahtani MS, Ahmad MZ, Ahmad J, Kotta S. 3D Printing in medicine: Technology overview and drug delivery applications. Ann 3D Print Med. 2021;4:100037 L THE PANACEA / VOLUME 2 2023 / 9 RESEARCH HIGHLIGHTS

Formulation and Characterisation of Juglone-Loaded Poloxamer-Based Hydrogels or Diabetic Wounds Ooi Ming Liang1, Nelli Giribabu2 and Shaik Nyamathulla1* 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia. 2Department of Physiology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia. Corresponding author*- [email protected] Background Diabetic wounds require a comprehensive wound care, its mismanagement could result in amputation, and other severe morbidities. Juglone, a natural phytoconstituent is with well-established antioxidant and antibacterial attributes. Poloxamers are thermosensitive polymers with excellent biocompatibility, high water absorption capability and are able to recruit immune cells to promote wound healing. Four formulations of Juglone were formulated, JPH1 (blank), JPH2 (0.05% w/w), JPH3 (0.25% w/w) and JPH4 (0.5 % w/w) and characterized for appearance, pH, texture and rheological properties. Formulations were homogenous, acidic, pseudoplastic and good texture to promote skin regeneration. Statistics from National Health and Morbidity Survey (2019) revealed that 3.9 million (18.3%) Malaysian adults are diabetic, 15% of them suffer from chronic wounds (Ministry of Health Malaysia, 2014). Chronic wounds compromise patients’ quality of life, and are associated with increased morbidity, mortality and healthcare costs. Existing wound dressings have limitations such as necessitating frequent change, stripping of newly formed epithelial layer upon removal and are expensive. This study is attempted to address the aforementioned limitations by formulating a new wound dressing hydrogel. Juglone is a phenolic and aromatic compound with broad spectrum antimicrobial effects towards bacteria, algae and fungi. It reduces oxidative stress generated by excessive reactive oxygen species (ROS) production in chronic wounds (Cano Sanchez et al., 2018). Hydrogels are extensively used to create a favourable humid environment for wound healing, ease of removal, cooling effect and reducing the risk of secondary injury (Xiang et al., 2020). In this study, poloxamer-based hydrogels containing juglone were formulated and evaluated for their quality parameters such as appearance, pH, texture and rheological properties to develop it as a candidate in chronic wound management. About 4% P-407, 2% w/v carboxymethylcellulose, 2% v/v P188 and 0.2% w/v benzoic acid were dissolved through continuous stirring and homogenisation at 200 rpm for 30 minutes. Juglone was loaded into the poloxamerbased gel and evaluated. All four hydrogel formulations (JPH1 to JPH4) loaded with juglone were homogeneous, transparent, colourless, yellowish to dark brown with increased Juglone concentration. The pH of the formulations ranged from 4.80-5.36, the low pH could be due to the addition of benzoic acid. Healthy skin is slightly acidic with the pH ranging from 4.0 to 7.0 due to skin secretions which protect the skin from microbes (Lambers et al., 2006; Kumar et al., 2021). Hence, a slightly acidic dressing favours wound healing. The texture of a hydrogel is dependent on its composition and concentration (Chen et al., 2013). The hardness of a gel usually dictates the force required to remove the gel from its container (Bansal et al., 2009). The poloxamer-based hydrogels have low hardness and adhesiveness when compared to Carbopol-based and chitosan-based hydrogels. Low hardness is desirable, the hardness values in our study (0.10 ± 0.006 N) were considerably lower. Rheograms of all formulations exhibited pseudoplastic behaviour at 25 and 32 ℃. A pseudoplastic system displays shear-thinning effects, whereby the viscosity decreases and the shear stress increases as the shear rate increases (Osmani et al., 2015). The polymer chains start aligning themselves in the long axes in the direction of flow in response of increasing shear stress. This leads to the lowering of internal resistance and eventually the viscosity (Fathalla et al., 2017). A gel displaying pseudoplastic behaviour is ideal for topical use as shear lowers the viscosity and increases the spreadibility. Over all, the gels prepared were uniform, transparent with acidic pH (4.80- 5.36), which is suitable for skin application. JPH4 demonstrated the best texture profile at acceptable hardness (0.13 ± 0.006 N), highest adhesiveness (-0.28 ± 0.015 N.s), cohesiveness (1.32 ± 0.035) and springiness (0.98 ± 0.025 mm). However, further characterisation is needed to analyse juglone-polymer compatibility and in vivo wound healing capabilities of the gels. References 9. Bansal, K., Rawat, M. K., Jain, A., Rajput, A., Chaturvedi, T. P., & Singh, S. (2009). Development of satranidazole mucoadhesive gel for the treatment of periodontitis. AAPS PharmSciTech, 10(3), 716-723. 10. Cano Sanchez, M., Lancel, S., Boulanger, E., & Neviere, R. (2018). Targeting oxidative stress and mitochondrial dysfunction in the treatment of impaired wound healing: A systematic review. Antioxidants, 7(8), 98. 11. Chen, J., Zhou, R., Li, L., Li, B., Zhang, X., & Su, J. (2013). Mechanical, rheological and release behaviors of a poloxamer 407/poloxamer 188/Carbopol 940 thermosensitive composite hydrogel. Molecules, 18(10), 12415-12425. 12. Fathalla, Z. M., Vangala, A., Longman, M., Khaled, K. A., Hussein, A. K., El-Garhy, O. H., & Alany, R. G. (2017). Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies. European Journal of Pharmaceutics and Biopharmaceutics, 114, 119-134. 13. Kumar, N., Kumar, S., Singh, S. P., & Rao, R. (2021). Enhanced protective potential of novel citronella essential oil microsponge hydrogel against Anopheles stephensi mosquito. Journal of Asia-Pacific Entomology, 24(1), 61-69. 14. Lambers, H., Piessens, S., Bloem, A., Pronk, H., & Finkel, P. (2006). Natural skin surface pHis on average below 5, which is beneficial for its resident flora. International Journal of Cosmetic Science, 28(5), 359-370. 15. Ministry of Health Malaysia. (2014). Wound Care Manual (1st ed.). Putrajaya: Ministry of Health Malaysia. 16. Osmani, R. A. M., Aloorkar, N. H., Ingale, D. J., Kulkarni, P. K., Hani, U., Bhosale, R. R., & Dev, D. J. (2015). Microsponges based novel drug delivery system for augmented arthritis therapy. Saudi Pharmaceutical Journal, 23(5), 562-572. 17. Xiang, J., Shen, L., & Hong, Y. (2020). Status and future scope of hydrogels in wound healing: Synthesis, materials and evaluation. European Polymer Journal, 109609-109621 L 10 / THE PANACEA / VOLUME 2 2023 RESEARCH HIGHLIGHTS

Microneedle For Drug Delivery Kirthana Gopal1, Syed Mahmood1*, Zarif Mohamed Sofian1 1 Department of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur 50603, Malaysia *Correspondence to* : [email protected] Abstract Conventional routes of drug administration have acceptable therapeutic response however faces challenges such as poor patient compliance, poor bioavailability, enzymatic and chemical degradation and more. Microneedles are a new smart approach composed of micron-size needles to mediate the localized delivery of therapeutic molecules. It is a painless, less invasive, and highly versatile drug delivery system that eases self-administration, with high drug bioavailability. This review briefly introduces the application of microneedles in transdermal and oral drug delivery. Additionally, different types of microneedles and their advantages as well as drawbacks are introduced, along with recent biological applications. Research being conducted are proof of concept for application of microneedles in drug delivery, however, further in depth research in human clinical trials and development of cost-effective largescale manufacturing process should be established for successful commercial translation of microneedles. Keywords: Drug delivery; microneedles; solid microneedles, dissolving microneedles; coated microneedles; hollow microneedles. Introduction Drugs and therapeutics have been delivered in various routes of administration throughout the years to treat illnesses and improve quality of life. The most used routes of administration include oral, parenteral, nasal, transdermal and many more. These conventional routes of administration have acceptable ease of administration and effectiveness, however there are several significant challenges including first pass metabolism, poor patient compliance and poor bioavailability. Therefore, new drug delivery systems are being explored extensively to improve absorption of drug, promote rapid onset of action, and potentially overcome the challenges faced by conventional routes of administration (Ruiz & Scioli Montoto, 2018). Microneedles (MNs) are a smart approach composed of micron-size needles organized in a single structure or arranged in small arrays to mediate the localized delivery of therapeutic molecules, enhancing drug delivery. These micro projections generally present dimensions around 50 to 250μm in width and length ranging from few micro-meters to those as long as 1500μm. In general, the MNs application aims to create a transport pathway for the delivery of therapeutic molecules, bypassing the external barriers that limit the therapeutics penetration into the target tissue. Further, the MNs devices are compatible with the delivery of both small and macromolecular therapeutics such as small drugs, proteins, genetic materials or even nanomedicines. Additionally, MNs are highly versatile and are regarded as less painful, damaging, and safer to use, when compared to conventional needles. Moreover, MNs can be produced using several different materials and fabrication methods. This results in a wide variety of MNs designs that in general are categorized as solid MNs, drug coated MNs, dissolving MNs, and hollow MNs (Moreira et al., 2019). Microneedle for transdermal drug delivery Transdermal Drug Delivery Systems (TDDS) are defined as self-contained, discrete dosage forms when applied to the intact skin, deliver the drug through the skin at a controlled rate to the systemic circulation. TDDS are dosage forms designed to deliver a therapeutically effective amount of drug across a patient’s skin. The main objective of the TDDS is to deliver drugs into systemic circulation through skin at a predetermined rate with minimal inter and intra patient variation. Currently transdermal delivery is one of the most promising methods for drug application. Transdermal delivery also has advantages over hypodermic injections, which are painful, generate dangerous medical waste and risk disease transmission by needle re-use, especially in developing countries. In addition, transdermal systems are non-invasive and can be selfadministered (Prausnitz & Langer, 2008). The stratum corneum is the outermost layer of skin and principal barrier for the penetration of drug. Dermis is composed of a matrix of connective tissue, which contains blood vessels, lymph vessels and nerves. The cutaneous blood supply thus keeps the dermal concentration of a permeant very low and the resulting concentration difference across the epidermis provides the essential concentration gradient for transdermal permeation. The hypodermis or subcutaneous fat tissue supports the dermis and epidermis. It serves as a fat storage area. It carries principal blood vessels and nerves to the skin and may contain sensory pressure organs. For TDDS, the drug must penetrate through all these three layers and reach into the systemic circulation while in the case of topical drug delivery only, penetration through stratum corneum is essential. Then retention of drug in skin layers is desired (Sharma et al., 2011). MNs can bypass the mechanical barrier of stratum corneum that restricts penetration of therapeutics to the target tissue, thus creating a transport pathway for therapeutic molecules delivery thereby improving drug delivery. Therefore, MNs for TDDS provides rapid onset of action through the lymphatic vessels and capillary bed in the dermis. MNs also avoids first pass metabolism and provide high drug bioavailability. The small size and length of MNs renders them painless and safe as well as promotes self-administration, thereby improves patient compliance and safety. However, there are some challenges and limitations that needs to be considered in application of MNs for drug delivery. The small size of MNs limits the dosage of drug, and sophisticated technologies and manufacturing process is needed to manufacture MNs with reproducibility. The application of MNs on the skin could lead to breakage, allergy, or temporary inflammation as well (Jung & Jin, 2021). In 2021, Chang et al., designed and fabricated cryogenic MN patches for transdermal cell delivery. Mice with subcutaneous melanoma tumours showed higher antigen specific immune responses and demonstrated slower tumour growth with administration of cryomicroneedles containing ovalbumin pulsed dendritic cells. This confirmed proof of concept that biocompatible MNs can facilitate minimally invasive transdermal cell delivery. THE PANACEA / VOLUME 2 2023 / 11 RESEARCH HIGHLIGHTS

Microneedles for oral drug delivery Oral route of administration for drugs is the most desirable and convenient for both patients and healthcare professionals compared to parenteral route. However, oral drug delivery is not ideal for proteins, peptides, vaccines, monoclonal antibodies, and other biological drugs as it suffers from enzymatic and chemical degradation in the gastrointestinal tract as well as low permeability across the intestinal epithelium, resulting in poor absorption and bioavailability (Lee & Prausnitz, 2018). In 2015, Traverso et al., developed a MN pill for oral delivery of biologic drugs. The pills were coated with pH responsive coating which dissolved once it reached the target location in the GI tract releasing the MN. The MNs penetrated the tissue, and the drug was released from the needle in a controlled rate. The bioavailability of insulin, the biologic drug was proven to be sufficient when administered via a MN pill in the GI tract as the blood glucose response kinetics significantly improved in comparison to subcutaneous injection. In 2019, Abramson et al., fabricated a luminal unfolding MN injector (LUMI) for delivery of macromolecules orally. The LUMI device was ingested in waterproof enteric capsules. Once it reached the small intestine, the device actuated and unfolded thereby injecting the MN loaded with drugs into the intestinal epithelium wall which dissolved releasing the drug. The LUMI device demonstrated effective and safe drug delivery into the small intestine in the preclinical in vivo studies using swine. Types of Microneedles There are different types of MNs with unique properties and mechanisms of action in drug delivery. MNs can be fabricated using different materials including polymers, silicon, glass, ceramic or metal depending on their use. MNs are generally classified into 4 groups which are solid MNs, dissolving MNs, hollow MNs and coated MNs. Solid microneedles The structure of solid MNs is used as pretreatment for skin and designed to pierce into the stratum corneum to create micro pores in the skin and are then removed from the skin surface. Solid MNs work on poke and patch principle as it creates microchannels where the drug patch is applied to improve drug permeability through diffusion from the formulation into the viable epidermis thereby improving the bioavailability of the drug (Kulkarni et al., 2022). Solid MNs have superior mechanical strength, sharper tips and are easy to manufacture. However, solid MNs do damage the skin and create micro-channels that need to be closed using termination therapy to prevent introduction of toxic materials and avoid possible infections (Aldawood et al., 2021). In 2017, Li et al., fabricated solid polylactic acid (PLA) MNs of 600µm height, 800µm depth and 256 MNs per cm2 density which showed good mechanical stability to pierce the SC and enhanced drug permeation. Solid MNs only have the potential to be used in transdermal drug delivery. Dissolving microneedles Dissolving microneedles (DMNs) facilitate rapid release of macromolecules. DMNs are polymeric, microscopic needles that encapsulate pharmaceuticals within their matrix. Insertion of DMNs into the skin or tissue catalyzes the degradation of the polymeric compound, thereby releasing the drug for systemic or local delivery. Unlike hypodermic injections, DMNs are fully biocompatible and generate no biohazardous sharps waste. Moreover, DMNs have also been shown to be more dose-effective compared with subcutaneous immunizations. DMNs deliver drugs into skin based on the mechanism of the “poke-and-release” method. Drugs are usually encapsulated within MNs, and then the drug-releasing is realized when MNs completely degrade or dissolve in the skin or tissue. These MNs have various advantages, such as being easily made, convenient, one step easy application and high drug loading (He et al., 2019). In 2021, He et al., designed DMNs for enhanced dermal delivery of propranolol hydrochloride for treatment of infantile hemangioma by two-step casting method. DMN loaded with the drug showed good mechanical strength for 1 penetration and significantly improved permeability and skin retention of propranolol. DMNs can be used in both transdermal and oral drug delivery as it does not leave behind any biologically harmful waste after dissolution of the MNs. Coated microneedles Coated MNs comprise of a solid MN as base that is coated with the drug solution or dispersion. Coated MNs work on the principle of ‘coat and poke’ where the drug coating layer dissolves rapidly into the skin upon insertion and the MN base is removed from skin after dissolution of the drug layer (Kulkarni et al., 2022). The advantages of coated MNs are rapid drug delivery and fast onset of action upon insertion in the skin and it has an easy one step application. However, the success of coated MNs in drug delivery depends on the ability to coat an accurate predetermined amount of drug and controlled drug layer onto the MNs. Coated MNs also only delivers small amount of drug due to their design therefore it is also suitable for highly potent drug that requires low doses (Chen et al., 2013). In 2016, Jain et al., fabricated 5-aminolevulinic acid (5-ALA) coated MNs for photodynamic therapy of skin tumours. The 5-ALA was naturally converted into a photosensitizer named protoporphyrin IX (PPIX) and delivery of 5-ALA was enhanced through coated MNs. Hollow microneedles The design of hollow MNs have internal chamber or lumen approximately 50 to 70 µm in diameter in which the drug solutions are loaded. Hollow MNs are a scaled down version of the conventional hypodermic needle, and it works on the principle of ‘poke and flow’. The drug is delivered from the MN based on the pressuredriven flow of the drug solution in the internal chamber. Hollow MNs can load large amount and dosage of drugs into the lumen therefore it is suitable for delivery of high molecular weight compounds like vaccines and proteins. It is having the ability to deliver substantial doses of drug into the viable epidermis or dermis region and control drug release over time. The fabrication process of hollow MNs is more complicated due to the structure of the needles and its fragility (Chen et al., 2022). In 2018, van der Maaden et al., designed, and fabricated hollow MN of liposomal HPV synthetic long peptide vaccine which demonstrated strong functional cytotoxic and T-helper responses in mice. It also required much lower volumes to induce the responses than the classic intradermal immunization. Therefore, serves as proof of concept that hollow MNs have the potential for delivery of therapeutic cancer vaccines in a pain free and minimally invasive manner. Conclusion Delivery of drugs and therapeutics directly Figure 1 Schematic illustration of the different types of microneedles with transdermal drug delivery to the target site is highly desirable as it pattern. (A) Solid MN; (B) Dissolving MN; (C) Coated MN and (D) Hollow MN. 12 / THE PANACEA / VOLUME 2 2023 RESEARCH HIGHLIGHTS

improves absorption of drug, promote rapid onset of action, improves efficacy, and overcome challenges encountered with administration of drugs systemically. MNs are a smart and powerful approach to deliver the drugs by temporarily permeating the barrier layer such as the epithelium or endothelium. The development of marketable MNs based delivery for drugs is likely in the near future. Extensive research is actively being conducted for the efficient application of MNs in TDDS, including other routes of delivery like oral route, that can expand the market for delivery of various therapeutics including but not limited to macromolecules, hydrophilic molecules, proteins, and vaccines. Several research have established the effectiveness of MNs however there are shortcomings that limits the commercial translation of MNs for drug delivery such as the need of in depth human clinical trials, design and development of cost-effective large-scale manufacturing process. This shortcoming needs to be addressed wisely and promptly for successful development of commercial MN based drug delivery technology which will lead to improved prevention, diagnosis, and management of illness, along with improved quality of life for patients worldwide. REFERENCES 18. Abramson, A., Caffarel-Salvador, E., Soares, V., Minahan, D., Tian, R. Y., Lu, X., Dellal, D., Gao, Y., Kim, S., Wainer, J., Collins, J., Tamang, S., Hayward, A., Yoshitake, T., Lee, H.-C., Fujimoto, J., Fels, J., Frederiksen, M. R., Rahbek, U., … Traverso, G. (2019). A luminal unfolding microneedle injector for oral delivery of macromolecules. Nature Medicine, 25(10),1512–1518. https://doi. org/10.1038/s41591-019-0598-9 19. Aldawood, F. K., Andar, A., & Desai, S. (2021). A comprehensive review of Microneedles: Types, materials, processes, characterizations and applications. Polymers, 13(16), 2815. https://doi. org/10.3390/polym13162815 20. Chang, H., Chew, S. W., Zheng, M., Lio, D. C., Wiraja, C., Mei, Y., Ning, X., Cui, M., Than, A., Shi, P., Wang, D., Pu, K., Chen, P., Liu, H., & Xu, C. (2021). Cryomicroneedles for Transdermal Cell Delivery. Nature Biomedical Engineering, 5(9),1008–1018. https://doi.org/10.1038/s41551-021-00720-1 21. Chen, J., Qiu, Y., Zhang, S., Yang, G., & Gao, Y. (2013). Controllable coating of microneedles for transdermal drug delivery. Drug Development and Industrial Pharmacy, 41(3), 415–422. https://doi.org/10.3109/0363 9045.2013.873447 22. Chen, J., Ren, H., Zhou, P., Zheng, S., Du, B., Liu, X., & Xiao, F. (2022). Microneedlemediated drug delivery for cutaneous diseases. Frontiers in Bioengineering and Biotechnology,10. https://doi.org/10.3389/ fbioe.2022.1032041 23. He, J., Zhang, Z., Zheng, X., Li, L., Qi, J., Wu, W., & Lu, Y. (2021). Design and Evaluation of Dissolving Microneedles for Enhanced Dermal Delivery of Propranolol Hydrochloride. Pharmaceutics,13(4),579. doi:10.3390/pharmaceutics13040579 24. He, J., Zhang, Z., Zheng, X., Li, L., Qi, J., Wu, W., & Lu, Y. (2021). Design and evaluation of dissolving microneedles for enhanced dermal delivery of propranolol hydrochloride. Pharmaceutics,13(4),579. https://doi.org/10.3390/ pharmaceutics13040579 25. Jain, A. K., Lee, C. H., & Gill, H. S. (2016). 5-aminolevulinic acid coated microneedles for photodynamic therapy of skin tumors. Journal of Controlled Release, 239, 72–81. https://doi.org/10.1016/j.jconrel.2016.08.015 26. Jung, J. H., & Jin, S. G. (2021). Microneedle for Transdermal Drug Delivery: Current Trends and Fabrication. Journal of Pharmaceutical Investigation,51(5),503–517. https://doi.org/10.1007/s40005-021-00512- 4 27. Kulkarni, D., Damiri, F., Rojekar, S., Zehravi, M., Ramproshad, S., Dhoke, D., Musale, S., Mulani, A. A., Modak, P., Paradhi, R., Vitore, J., Rahman, M. H., Berrada, M., Giram, P. S., & Cavalu, S. (2022). Recent advancements in microneedle technology for multifaceted biomedical applications. Pharmaceutics, 14(5),1097. https://doi.org/10.3390/ pharmaceutics14051097 28. Lee, J. W., & Prausnitz, M. R. (2018). Drug delivery using microneedle patches: Not just for skin. Expert Opinion on Drug Delivery, 15(6), 541–543. https://doi.org/10.1 080/17425247.2018.1471059 29. Li, Q. Y., Zhang, J. N., Chen, B. Z., Wang, Q. L., & Guo, X. D. (2017). A solid polymer Microneedle Patch pretreatment enhances the permeation of drug molecules into the skin. RSC Advances, 7(25), 15408–15415. https://doi.org/10.1039/c6ra26759a 30. Moreira, A., Rodrigues, C., Jacinto, T., Miguel, S., Costa, E., & Correia, I. (2019). Microneedle-based delivery devices for cancer therapy: A review. Pharmacological Research, 148, 104438. doi: 10.1016/j. phrs.2019.104438 31. Nikhil Sharma, Geta Agarwal, A. C. Rana, Zulfiqar Ali Bhat, Dinesh Kumar“A Review: Transdermal Drug Delivery System: A Tool For Novel Drug Delivery System”,Int. J. Drug Dev. & Res., Jul-Sep 2011, 3(3): 70-84 32. Prausnitz, M., & Langer, R. (2008). Transdermal drug delivery. Nature Biotechnology, 26(11), 1261-1268. doi: 10.1038/nbt.1504 33. Ruiz, M. E., & Scioli Montoto, S. (2018). Routes of Drug Administration. ADME Processes in Pharmaceutical Sciences, 97–133. https://doi.org/10.1007/978-3-319- 99593-9_6 34. Traverso, G., Schoellhammer, C. M., Schroeder, A., Maa, R., Lauwers, G. Y., Polat, B. E., Anderson, D. G., Blankschtein, D., & Langer, R. (2015). Microneedles for drug delivery via the gastrointestinal tract. Journal of Pharmaceutical Sciences, 104(2), 362–367. https://doi.org/10.1002/jps.24182 35. van der Maaden, K., Heuts, J., Camps, M., Pontier, M., Terwisscha van Scheltinga, A., Jiskoot, W., Ossendorp, F., & Bouwstra, J. (2018). Hollow Microneedle-mediated micro-injections of a liposomal HPV E743–63 synthetic long peptide vaccine for efficientinduction of cytotoxic and T-helper responses. Journal of Controlled Release, 269, 347–354. https://doi.org/10.1016/j. jconrel.2017.11 L THE PANACEA / VOLUME 2 2023 / 13 RESEARCH HIGHLIGHTS

Nose-to-brain drug delivery: Challenges and future prospects towards brain targeting therapy Zarif Mohamed Sofian*, Syed Mahmood Department of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya corresponding to*: [email protected] building blocks (Fig. 1). The nanoscale particle sizes of NP provide greater surface areas that can lead to increased drug solubility, stronger interaction with mucosa, or better permeation. At the same time, the use of NP can protect therapeutic agents from degradation and prevent their extracellular transport by outgoing transporters. Many studies have shown improved permeability and absorption of drugs, their uptake in the olfactory region, and their access and accumulation into the CNS when administered using nanoparticle-based systems via the noseto-brain route in vivo. Despite the various advantages of NP, the clinical translation of nose-to-brain delivery of NP still has a long way to go. Indeed, mucociliary clearance, enzymatic degradation of the drug, scaling-up and stability of the nanoformulation, low efficiency of NP translocation, mucosal toxicity, and brain neurotoxicity are typical limitations of this drug delivery approach. In particular, the long-term biosafety of NP is a relevant concern, and developing nanocarriers with low or no toxicity to the organism and the environmentis one ofthe most significant challenges associated with their design. The administration of therapeutics to the central nervous system (CNS) is primarily regulated by the blood-brain barrier (BBB), a structure that prevents the free passage of foreign molecules from the blood into the brain’s extracellular fluid. To treat brain diseases/disorders that affect millions of people worldwide, the administered drug must reach the brain at therapeutic levels. Although the currently available treatments for such diseases are to some extent effective, the drug’s systemic distribution is often linked with severe side effects and off target distribution that can negatively affect patients’ quality of life. In this context, therapeutics delivery via nose-to-brain offers a new promising alternative from the traditional modes of drug administration e.g., parenteral and oral routes. The nasal cavity presents distinct anatomical attributes that can facilitate drug administration, leading to a less intrusive pathway, ensuring a rapid onset of action, and bypassing the first-pass metabolism in the liver. With a surface area of around 160 cm2 (96,000 cm2 comprising the microvilli), this route of drug administration has been extensively studied to deliver topical and systemic treatments. Meanwhile, the olfactory region, providing direct access to the brain, has an area of only around 5 cm2 (3,000 cm2 comprising the microvilli). Furthermore, the intranasal cavity has a high-density microvasculature partly responsible for drug absorption and distribution. However, the intricacies of nasal physiology introduce certain hurdles that necessitate careful consideration during the development of drug formulations for this route. These include limited volume of formulation that can be applied into the nose, mucociliary clearance, presence of a mucus layer, and local enzymes are some of the factors that can hamper drug absorption through this route. In light of this, nanoparticlebased drug delivery systems have shown to be a valuable tool to promote drug accumulation in the CNS through an increased permeation across the olfactory region. Polymeric based nanoparticles (NP) are perhaps the most popular, versatile and promising nanocarriers studied for therapeutics brain delivery through noseto-brain pathway owing to their chemical versatility, high drug loading capacity, and ease of surface functionalization with targeting ligands. Different types of structures could be achieved using polymers (either natural or synthetic) as References: 1. Vohra, M. et al. (2023) Formulation strategies for nose-to-brain drug delivery in Alzheimer’s disease. Health Sciences Review, 6, 100075. 2. Emad, N.A. et al. (2021) Recent progress in nanocarriers for direct nose to brain drug delivery. Journal of Drug Delivery Science and Technology, 64, 102642. 3. Awad, R. et al. (2023) Polymeric nanocarriers for nose-to-brain drug delivery in neurodegenerative diseases and neurodevelopmental disorders. Acta Pharmaceutica Sinica B, 13, 1866-1886 L Fig. 1. Different explored strategy to ameliorate nose-to-brain drug delivery using polymeric nanoparticles NP. 14 / THE PANACEA / VOLUME 2 2023 RESEARCH HIGHLIGHTS

Anti-microbial sutures: An overview Chin Sek Peng* Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, 50603, Kuala Lumpur, Malaysia *[email protected] Sutures are pivotal in facilitating wound healing. Anti-microbial sutures coated with antiseptics such as triclosan and chlorhexidine have been used to minimise the risk of surgical site infection (SSI). The emergence of resistant strains has affected the effectiveness of antisepticbased sutures; hence, the development and advancement of alternative antimicrobial sutures are in the spotlight. There are two types of sutures, absorbable and non-absorbable sutures. Several approaches have been explored to incorporate the anti-microbial compounds on the sutures, such as dip-coating, surface modification, compound immobilisation, blending, and compounding. The dip-coating method is the most popular approach as it is more cost and technique friendly than other methods, and it does not change the mechanical properties of the suture (1, 2). The anti-microbial compounds used in developing anti-microbial sutures include antiseptics, natural products, antibiotics, nanoparticles, and biotechnological products. Triclosan- and chlorhexidine-based sutures are the only commercially available anti-microbial sutures for medical use. Triclosan is a broad-spectrum and lipid-soluble chlorinated phenoxyphenol chemical compound widely used to formulate personal care and household products (3). It is also a topical decontamination agent for hospitalised patients with methicillin-resistant S. aureus (MRSA) (4). The high exposure to triclosan through daily consumables has caused triclosan resistance in some bacteria strains (5) and indirectly contributes to the resistance to multiple antibiotics (6). Similarly, chlorhexidine is a broad-spectrum antiseptic used since the late 1940s. The chlorhexidine is effective against MRSA, S. epidermidis, methicillin-resistant S. epidermidis (MRSE), and E. coli. Several studies have reported the anti-microbial properties of chlorhexidine-coated suture on inhibiting S. epidermidis, E. coli, Micrococcus luteus, and Bacillus subtilis for up to seven days, using low concentration, and without compromising the tensile properties of the sutures (7). Apart from antiseptics, plant extracts have been researched to be used as an anti-microbial coating agent on the suture. The natural products used are grapefruit seed extract, aloe vera, chitosan, turmeric, clove oil, and eugenol. A recent study using plasma functionalisation and immobilisation of aloe vera and silver particles on the suture demonstrated superior bacteriostatic and bactericidal activities against E. coli and S. aureus in an animal model (8). Nanoparticles are not only being explored in cancer treatment and targeted drug delivery but have also found it’s used in coated sutures. As early as 2011, researchers started coating Ag nanoparticles on polyamide sutures. The Ag nanoparticles coated sutures demonstrated a reduction in bacterial colonies for more than 70%, up to 72 hours (9). A recent study showed a new direction of coated suture where a combination of coating material could be a mixture of nanoparticles, natural compounds, and antiseptics that show synergistic antimicrobial action (10). Apart from antiseptics, natural products, and nanoparticles, coating antibiotics on the suture were also attempted. The antibiotics have made the suture functional in reducing bacterial colonisation for longer. The examples of antibiotics researched are gentamicin, s u l f a m e t h o x a z o l e - t r i m e t h o p r i m , ciprofloxacin, and levofloxacin (11). The antibiotics-based suture can potentially be used as a prophylactic measure as it has been shown to prevent ocular infection in rats (12). Synthetic peptides and recombinant proteins are the other biotechnological products being explored to be coated on the sutures. It has been reported that spider silk and alphadefensin protein coated on the suture using the dip-coating method reduced the viability, adherence, and biofilm formation of MRSA and E. coli (13). The only two currently available antimicrobial sutures will not be sufficient to fight the battle against bacterial resistance. The next generation of bioactive functional sutures must not only be effective against SSI without classical antibiotics, but they also have to be feasible to be fabricated with fewer complex processes and economical. Attaining a zero SSI rate would be possible with continuous effort in researching new materials or novel coating methods/ technology in developing anti-microbial sutures, together with good infection control practice in clinical settings. *This overview is an excerpt from Chua RAHW, Lim SK, Chee CF, Chin SP, Kiew LV, Sim KS, Tay ST. Surgical site infection and development of antimicrobial sutures: a review. Eur Rev Med Pharmacol Sci. 2022 Feb;26(3):828-845. References: 1. Champeau M, Thomassin JM, Tassaing T, Jérôme C. Current manufacturing processes of drug-eluting sutures. Expert Opin Drug Deliv 2017; 14: 1293-1303. 2. Viju S, Thilagavathi G. Effect of chitosan coating on the characteristics of silkbraided sutures. J Ind Text 2012; 42: 256- 268. 3. Bhargava HN, Leonard PA. Triclosan: applications and safety. Am J Infect Control 1996; 24: 209-218. 4. Z AD, Morrison D, Philpott-Howard J. Small colony variants and triclosan resistance in five inter- national clones of methicillinresistant Staphylococcus aureus. J Mol Biol Res 2017; 7: 112. 5. Russell AD. Whither triclosan? J Antimicrob Chemother 2004; 53: 693-695. 6. Copitch JL, Whitehead RN, Webber MA. Prevalence of decreased susceptibility to triclosan in Salmonella enterica isolates from animals and humans and association with multiple drug resistance. Int J Antimicrob Agents 2010; 36: 247-251. 7. Márquez Y, Cabral T, Lorenzetti A, Franco L, Turon P, del Valle LJ, Puiggalí J. Incorporation of biguanide compounds into poly(GL)-b-poly(GL- co-TMC-co-CL)- b-poly(GL) monofilament surgical sutures. Mater Sci Eng C Mater Biol Appl 2017; 71: 629-640. 8. Anjum S, Gupta A, Kumari S, Gupta B. Preparation and biological characterisation of plasma functionalised poly(ethylene terephthalate) anti-microbial sutures. Int J Polymer Mater Po 2020; 69: 1034-1042. 9. Augustine R, Rajarathinam K. Synthesis and characterisation of silver nanoparticles and its immobilisation on alginate coated sutures for the prevention of surgical wound infections and the in vitro release studies. Int J Nanodimens 2012; 2: 205-212. 10. Edis Z, Haj Bloukh S, Ibrahim MR, Abu Sara H. “Smart” anti-microbial nanocomplexes with potential to decrease surgical site infections (SSI). Pharmaceutics 2020; 12. 11. LiuS,YuJ,LiH,WangK,WuG,WangB,Liu M, Zhang Y, Wang P, Zhang J, Wu J, Jing Y, Li F, Zhang M. Controllable drug release behavior of polylactic acid (PLA) surgical suture coating with ciprofloxacin (CPFX)— polycaprolactone (PCL)/polyglycolide (PGA). Polymers (Basel) 2020; 12. 12. Parikh KS, Omiadze R, Josyula A, Shi R, Anders NM, He P, Yazdi Y, McDonnell PJ, Ensign LM, Hanes J. Ultra-thin, high strength, antibiotic-eluting sutures for prevention of ophthalmic infection. Bioeng Transl Med 2020: e10204. 13. Franco AR, Fernandes EM, Rodrigues MT, Ro- drigues FJ, Gomes ME, Leonor IB, Kaplan DL, Reis RL. Anti-microbial coating of spider silk to prevent bacterial attachment on silk surgical sutures. Acta Biomater 2019; 99: 236-246 L THE PANACEA / VOLUME 2 2023 / 15 RESEARCH HIGHLIGHTS

Centella asiatica: A Current Trend In Cosmetics With Therapeutic Potential Rozana Othman* and Muhammad Aiman Irfan Ibrahim Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya Coressponding author* - [email protected] Centella asiatica, apart from being consumed in diets, is traditionally used to treat various disorders. Nowadays, it is well known to soothe skin conditions, credited to the plenty of marketing from cosmetic industries. This article will review available data on whether the claim of the herb’s therapeutic potential to heal skin ailments is justifiable. Centella asiatica, also locally known as Pegaga (other names: Mandukaparni, Gotu Kola, Tiger grass, Gong Gen, and Indian pennywort), is a customary green in Malaysian diets, believed to provide numerous health benefits. It is a perennial plant belonging to the Apiaceae family, growing in a marshy environment of tropical and subtropical climates of Southeast Asia and India, besides some temperate regions, including countries of Japan, Korea, and China. Historically, ethnomedicine practitioners used it to remedy health issues, which include diabetes, Alzheimer, Parkinson’s disease, anal fissure, seizure, tumor, nervous system and sleep disorders, psychosis, and circulatory, respiratory, and gastrointestinal ailments [1 – 3]. Perhaps nowadays, it is notably known among the general population to heal dermatological problems. Some examples of its use in skin conditions are relieving scratches, an anti-inflammatory agent, and minor and hypertrophic wound healing [1 – 3]. Therefore, it has unsurprisingly become a current trend in cosmetics, particularly Korean beauty products marketed to soothe various common skin concerns experienced by consumers, such as acne The essential components isolated from C. asiatica are centelloids (triterpenoid saponins account for 1% - 8% of all constituents). The centelloids quantity may vary depending on the herb’s origin. The essential centelloids, attributed to their pharmacological activity, are asiaticoside, asiatic acid, madecassoside, and madecassic acid. Other naturally occurring centelloids in the herb include triterpenic acids: Brahmic acid, madasiatic acid, terminolic acid, and centellic acid, besides their respective glycosides: brahminoside, madasiaticoside, and centelloside. Besides those named above are volatile oils, flavonoids, tannins, phytosterols, amino acids, and sugars [1, 2]. Toxicologically, no significant adverse effects have been reported, neither in oral nor topical use. However, a local allergic reaction or burning sensation may happen, particularly from topical application [1, 2]. The herb is effective for infected wounds, burns, and postoperative hypertrophic scars, which can be attributed to the herb’s triterpenoid saponins content [2]. The healing property is evident in numerous in vitro and in vivo studies reported. A study using an oral madecassoside in a mouse model for 20 days demonstrated remarkably burn wound healing. The mechanism proposed was the triterpenoid increases the antioxidant activity, collagen synthesis, and angiogenesis. Another two in vivo animal studies using topical asiaticoside, one on a rat and another on a guinea pig model, exhibited increasing amount of amino acid hydroxyproline content essential for collagen formation [1]. Despite of the various in vivo data supporting the wound healing properties of C. asiatica, limited clinical studies are available to back its usage in humans. It is common for C. asiatica to be included in cosmetics which are marketed to reduce acne, although most evidence is anecdotal. Acne is a typical skin inflammation affecting the pilosebaceous units of the skin. The main pathological factors required for acne development include irregular follicular desquamation, inflammation, increased sebum production, and particularly Propionibacterium acnes proliferation. Subsequently, inflammatory lesions will form due to follicular damage and leakage of bacteria, fatty acids, and lipids into the surrounding dermis [3]. Based on an in vitro experiment, C. asiatica extract demonstrated little antibacterial activity against P. acnes, despite the purified madecassoside showing otherwise. In P. acnes stimulated THP-1 human monocytic cells,the triterpenoid significantly inhibits the production of proinflammatory cytokine IL-1β, TLR2 expression, and nuclear translocation of Nuclear Factor kappa B, NF-κB [3]. 16 / THE PANACEA / VOLUME 2 2023 RESEARCH HIGHLIGHTS

In conclusion, it has been centuries since C. asiatica was used to treat various illnesses, particularly skin conditions, and nowadays, many researchers are working to prove these scientifically. However, most of these evidences are either in vitro or in vivo, which means the data are not directly applicable to human subjects. More clinical data are required to support this herb’s therapeutic potential in humans. Perhaps investigating the compounds present in the herb, specifically, the triterpenoids, is a better approach for two reasons: 1. the extract’s constituents may vary significantly depending on the herb’s origin, and 2. relatively higher chances of allergic reaction using its extract due to numerous compounds present References: 1. F. A. Torbati et. al., Pharmacological Properties of Plant-Derived Natural Products and Implications for Human Health, ed. G. E. Barreto and A. Sahebkar, Springer Nature, Switzerland, 1st edn, 2019, vol. 1308, ch. 25, p.451 – 499. 2. Bylka, W., Znajdek-Awiżeń, P., StudzińskaSroka, E., & Brzezińska, M. (2013). Centella asiatica in cosmetology. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 30(1), 46-49. 3. Kyoung Sik Park. (2021). Pharmacological Effects of Centella asiatica on Skin Diseases: Evidence and Possible Mechanisms. Evidence-Based Complementary and Alternative Medicine, 2021, 5462633, pp.8 Virtual Screening of Potential Drug-Like Inhibitors against SARS-COV-2 NSP12 RNA-Dependent RNA Polymerase NS Shafai1, CH Heh*1 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya Correspondence to* [email protected] Abstract Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is an infectious disease that emerged on late December 2019 and turned into a pandemic crisis. WHO reported that around 769 million COVID-19 confirmed cases, including about 6.95 million deaths globally until early August 2023 (WHO, 2023). To date, 13.5 billion COVID-19 vaccine doses have been administered. Even though WHO declared an end to COVID-19 as a public health emergency in May 2023, there is a need to find alternative treatment for COVID-19. Hence, the active site of NSP12 RNAdependent RNA polymerase (RdRp) of the SARS-CoV-2 virus was chosen as the drug target as it is the most accessible and conserved region of the virus. This study was conducted to investigate the potential drug-like inhibitors against SARS-CoV-2 RdRp by using virtual screening. The top 50 drug-like compounds were selected after being virtually screened from the MTiOpenScreen server (Labbe et al., 2015). They were subsequently subjected to thorough docking and analysis. This study used the crystal structure of SARS-CoV-2 RdRp (PDB ID: 7BV2) (Yin et al., 2020) as the drug target and the drug remdesivir was employed as the standard ligand. AutoDock Vina 1.1.2 (Trott & Olson, 2010) was hired to thoroughly dock the standard ligand and drug-like compounds towards the drug target with the exhaustiveness 200. The docking results were analysed by Discovery Studio Visualiser 4.5. From the analysis, the top 5 drug-like inhibitors will be identified through comparable binding affinity and accurate binding interaction towards the essential amino acid residues (ARG-555 and SER-759) of the drug target compared to the standard ligand. Hesperidine (Figure 1) was identified as the best drug-like potential inhibitor because it showed correct binding interactions towards the essential amino acid residues and binding energy of -9.7 kcal/mol. Nevertheless, this potential inhibitor still needs to undergo further in vitro and in vivo studies to validate its inhibitory activity and safety profile. Figure 1. The binding interaction of hesperidin at the binding pocket of SARSCoV-2 RdRp. The essential amino acids of the active site are highlighted in red boxes. References: 1. Labbe, C. M., Rey, J., Lagorce, D., Vavrusa, M., Becot, J., Sperandio, O., . . . Miteva, M. A. (2015). MTiOpenScreen: a web server for structure-based virtual screening. Nucleic Acids Res, 43(W1), W448-454. 2. Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem, 31(2), 455-461. 3. World Health Organization. (2023). WHO coronavirus disease (COVID-19) dashboard. https://covid19.who.int/ 4. Yin, W., Mao, C., Luan, X., Shen, D. D., Shen, Q., Su, H., . . . Xu, H. E. (2020). Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science, 368(6498), 1499-1504 L Figure 1 The binding interaction of hesperidin at the binding pocket of SARS-CoV-2 RdRp. The essential amino acids of the active site are highlighted in red boxes. THE PANACEA / VOLUME 2 2023 / 17 RESEARCH HIGHLIGHTS

Ergothioneine: “Longevity Vitamin” From Farm to Fork Chia Wei Phan1,2,3,* 1Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia 2Mushroom Research Centre, Universiti Malaya, 50603 Kuala Lumpur, Malaysia 3Clinical Investigation Centre (CIC), 5th Floor, East Tower, University Malaya Medical Centre, 59100 Kuala Lumpur, Malaysia * [email protected] Abstract This article highlights the beneficial effects of L-ergothioneine (EGT), which is an amino acid derivative only produced by fungi and certain microbes, in mitigating aging-related illnesses, especially neurodegenerative disorders. It has been shown to display antioxidative properties which reduce mitochondrial apoptosis induced by oxidants in the central nervous system. EGT, which has been coined as the “longevity vitamin” is proven to be essential for health, although sadly it cannot be synthesized by the body. Mushrooms, in which the EGT content varies, are still the main dietary source of EGT even though other foods also have it in relatively lower amounts. Keywords: aging, antioxidant, ergothioneine, fungi, mushroom, neurodegenerative L-Ergothioneine (EGT) is a histidinederived antioxidant which is first discovered in ergot fungus (Claviceps purpurea). The fact that EGT is stable in bodily pH makes it highly resistant to autoxidation, hence it can prevent cellular damages due to oxidation by scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS). Those molecules that cause oxidation, named oxidants, are produced as the byproducts of some normal cellular activities which accumulate with age [1]. Thus, oxidation is said to be one of the primary culprits of aging-related degenerations. Oxidants can inflict deterioration to neuronal cells through inducing mitochondrial apoptosis which is the programmed cell death. As a naturally occurring compound, EGT is widely studied to mitigate oxidative damage. However, EGT is produced only by fungi and certain types of microorganisms, meaning that the human’s body cannot produce EGT by itself, it must be sourced from dietary intake [2]. In physiological pH, EGT exists in its zwitterion form which cannot diffuse through the cell membrane by itself, thus needsaspecifictransporter.Inmammalian cell membranes, the protein transporter responsible for EGT intake to the cell is the EGT transporter (ETT) which is the product of the expression of Solute Carrier Family 22 Member 4 (SLC22A4) gene. This transporter was once named novel organic cation transporter (OCTN1) but has been changed to a more appropriate name due to its higher specificity to EGT [3]. EGT is largely expressed in erythroid progenitor cells, hence allowing the red blood cells to uptake EGT from dietary consumption within an hour [2]. The fact that EGT is evolutionarily conserved in all vertebrates, highlights the importance of EGT to the human biological systems. Various research showed that EGT level in the body can be correlated with various chronic neurodegenerative diseases, especially those related to aging. This is due to the ability of EGT to cross the blood brain barrier, making EGT a compound that can affect the brain directly. One study demonstrated that the amount of EGT in the blood becomes lesser as people aged, and the amount gets even lower in those who are suffering from cognitive disability [4]. Moreover, another study by Hatano et al. [5] concluded that EGT is present at a smaller level in people with Parkinson’s disease compared to those who do not have it, underlining the crucial role of EGT on the health of the central nervous system (CNS). Further support for the importance of EGT came from a study which indicated that the higher amount of EGT in the plasma correlates with reduced cardiovascular disease risk, mortality, and frailty in the elderly [6]. Kushairi et al. [2] from their study, found that EGT reduced the apoptosis rate in HT22 hippocampal cells which were exposed to hydrogen peroxide (H2O2), a type of oxidant. This research highlights the ability of EGT to act as a neuroprotective agent against oxidative stress. Lastly, the consumption of mushrooms, which is the main source of EGT, is shown to reduce the prevalence of mild cognitive impairment (MCI) in elderly people [7]. MCI, although mild as the name suggests, increases the risk of developing Alzheimer’s and dementia. Calling EGT a “longevity vitamin” as proposed by Ames [8] has created much debate since ergothioneine does not fit 18 / THE PANACEA / VOLUME 2 2023 RESEARCH HIGHLIGHTS

the general description of a vitamin since no immediate short-term impairment has been identified as the result of EGT deficiency.However,researchshowedthat EGT is in fact present in small amounts in all food, but the small amount is not enough to get rid of the long-term deficiency effect [9]. Hence, the said epithet may be in fact suitable for EGT. As mentioned earlier, mushrooms and microbes are the only ones that can synthesize EGT. While different kinds of mushrooms contain different amounts of EGT, a high level of EGT is found in king oyster mushroom (Pleurotus eryngii), grey oyster mushroom (Pleurotus pulmonarius), and shiitake (Lentinula edodes) (unpublished data from the author). Hence, judging from the fact that ergothioneine from mushrooms is bioavailable, mushrooms should be considered an excellent dietary source of this powerful antioxidant. Acknowledgment: The author would like to acknowledge Christophorus Manuel Heryanto, a student intern from UCSI University, for his assistance in drafting and creating the graphical abstract. References 1. A. Ionescu-Tucker, C. W. Cotman. Emerging roles of oxidative stress in brain aging and Alzheimer’s disease, Neurobiol Aging, 2021, 107, 86–95. 2. N. Kushairi, C. W. Phan, V. Sabaratnam, M. Naidu, P. David, Dietary amino acid ergothioneine protects HT22 hippocampal neurons against H2O2-induced neurotoxicity via antioxidative mechanism. Pharmanutrition, 2020, 13, 100214. 3. D. Gründemann, L. Hartmann, S. Flögel, The ergothioneine transporter (ETT): substrates and locations, an inventory, FEBS Lett., 2022, 596(10), 1252–1269. 4. I. K. Cheah, L. Feng, R. M. Tang, K. H. Lim, B. Halliwell, Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration? Biochem. Biophys. Res. Commun., 2016, 478(1), 162–167. 5. T. Hatano, S. Saiki, A. Okuzumi, R. P. Mohney, N. Hattori, Identification of novel biomarkers for Parkinson’s disease by metabolomic technologies, J. Neurol. Neurosurg. Psychiatry, 2015, 87(3), 295–301. 6. E. Smith, F. Ottosson, S. Hellstrand, U. Ericson, M. Orho-Melander, C. Fernandez, O. Melander, Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease, Heart, 2019, 106(9), 691–697. 7. L. Feng, I. K. M. Cheah, M. M. X. Ng, J. Li, S. M. Chan, S. L. Lim, R. Mahendran, E. H. Kua, B. Halliwell, The association between mushroom consumption and mild cognitive impairment: a community-based crosssectional study in Singapore. J. Alzheimer’s Dis., 2019, 68(1), 197–203. 8. B. N. Ames, Prolonging healthy aging: Longevity vitamins and proteins, Proc. Natl. Acad. Sci. U. S. A., 2018, 115(43), 10836– 10844. 9. R. B. Beelman, M. D. Kalaras, A. T. Phillips, J. P. Richie, Is ergothioneine a ‘longevity vitamin’ limited in the American diet? J. Nutr. Sci., 2020 L Defueling cancer: Lipid metabolism as an emerging therapeutic target for gynaecological cancers Azilleo Kristo Mozihim and Amira Hajirah Abd Jamil* Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya, 50603, Kuala Lumpur, Malaysai. Correspondence*: [email protected] Cancer cells undergo metabolic reprogramming to fuel the highenergy demand required for continual unregulated proliferation and growth; a trait now considered a hallmark of cancer. Cancer cells were recently established to dominate lipogenic metabolism to generate macromolecules as building blocks and large amounts of ATP for their fast proliferation even under a nutrient-deprived environment. Dysregulation of lipid metabolism, specifically via increased lipid uptake and synthesis of fatty acids, correlates with higher pathological stages and poorer prognosis in patients with gynaecological cancers. Therefore, limiting the uptake of lipids utilisation serves as an attractive therapeutic targets for these cancer types. Inhibiting key regulatory enzymes involved in lipid metabolism has also been shown to synergistically augment chemotherapeutic agents’ antitumour effects or overcome chemotherapeutic resistance in gynaecological cancers. In addition to the developing pharmacological inhibitors specifically targeting lipid metabolic enzymes, interest is growing in implementing diet-based interventions to supplement conventional chemotherapeutic regimes. 1.Limiting lipid uptake: CD36 Inhibition Lipid uptake is critical in supplying cancers with exogenous fatty acids (FAs) as fuel for their progression. Therefore, targeting the FAs transporter, CD36 could represent a promising therapeutic strategy in gynaecological cancers. One type of recently studied CD36 inhibitors, known as thrombospondin-1 (TSP-1) mimetic peptides, mimics the structure of CD36 ligands. Although many TSP-1 mimetics have been developed and studied, three were found to have antitumour activity in gynaecological cancers: ABT-510, ABT526 and ABT898. ABT510 is derived from the second properdin type I repeat of the NH2-terminal third of TSP-1 and, in mouse models, it inhibited the growth of epithelial ovarian cancer and increased its susceptibility to chemotherapeutic drugs. Despite its initial promise as a CD36 inhibitor to treat ovarian cancer, it was after that abandoned, as phase II clinical trials of ABT510 treatment in advanced renal cell carcinoma soft tissue sarcoma and metastatic melanoma showed it lacked sufficient clinical efficiency. ABT526 is a GVITRIR heptapeptide based on the second TSP-1 type 1 repeat. It exhibited antitumour activity in dogs bearing the metastasis of mammary carcinoma. More promising are secondgeneration TSP-1 mimics, such as ABT898, which are more stable and better tolerated. ABT898 regressed established ovarian tumours in animal models and significantly prolonged disease-free survival. Although it is established that the anti-tumorigenic properties of these TSP-1 mimics stem from the ensuing antiangiogenic effect upon CD36 binding, the inhibition of the FA uptake role of CD36 could also play a role in this regard. Indeed, the binding of TSP-1 to CD36 is known to inhibit the uptake of the longchain FA myristic acid and palmitic acid by CD36, operating in parallel with the antiangiogenic effects of TSP-1 in curbing the growth of gynaecological cancers. Recent studies have also implicated CD36 in promoting breast cancer resistance towards tamoxifen, a widely used selective ER modulator for treating ER+ breast cancer. CD36 protein expression was higher in tamoxifen-resistant MCF-7 (MCF7/TAMR) than in their non-resistant counterpart. Consequently, knocking down CD36 in MCF7/TAMR via siRNA restored sensitivity towards tamoxifen, as evidenced by tamoxifen regaining the ability to inhibit the growth of MCF7/TAMR. THE PANACEA / VOLUME 2 2023 / 19 RESEARCH HIGHLIGHTS

Collectively, it was established that utilising the tamoxifen-CD36 inhibitor combination might also require stratifying breast cancer patients based not only on tamoxifen resistance but also on both CD36 and ER expression levels. 2.Termination of lipid biosynthesis: Fatty Acid Synthase (FASN) Inhibition FASN catalyses the biosynthesis of saturated lipids from simple precursors via a process known as de novo lipogenesis. Evidence consistently suggests a protumorigenic role for FASN in gynaecological cancers. Pharmacologic FASN inhibitors are classified based on the FASN domain targeted, whether they target the β-ketoacyl synthase or thioesterase domain. Orlistat, a well-studied irreversible inhibitor of the thioesterase domain, exhibits antitumour properties in various breast and ovarian cancer cell lines. It is also a well-established anti-obesogenic agent, shown to reduce weight by about 3% in obese and overweight people compared with their placebo counterparts. This weight-losing effect suggests another mechanism through which orlistat may lower the risk of gynaecological cancers in concert with its FASN inhibitory activity. Natural FASN inhibitors are also available, the most studied of which is epigallocatechin gallate (EGCG), which has been shown to inhibit the growth of breast cancer cells in vivo and in vitro. Intriguingly, selective FASN inhibitor Fasnall operates by targeting co-factor binding to FASN, not by competing with the substrate intermediate of FASN. It had potent anticancer activity in various breast cancer cell lines and in MMTV-Neu in vivo model of HER2+ breast cancer, with favourable pharmacokinetics and tolerance profiles. Notably, it had a synergistic effect on tumour shrinkage when combined with carboplatin. TVB2640 is a first-in-class FA inhibitor used in a Phase I trial to investigate its efficiency in lowering metabolic markers associated with non-alcoholic fatty liver disease in obese men. TVB-2640 is part of an ongoing phase II clinical trial that seeks to determine its effectiveness with paclitaxel and trastuzumab in treating ER2+ breast cancer metastases. Interestingly, inhibition of FASN in gynaecological cancers by agents, such as cerulenin and C75, also impairs oestradiol-induced nuclear accumulation of ER and downregulates ER expression, reinforcing the antitumour effects of FASN inhibition by diminishing the protumorigenic signalling emanating through the ER pathway, which could also reduce the impact of oestradiol-induced upregulation of FASN. Coupling FASN inhibitors to inhibitors of aromatase, the enzyme converting androgens into oestrogens, could serve as potential therapeutic strategy in aromatase inhibitor-treated ER+ breast cancer patients to recurrence, which is due to the ability for aromatase inhibitors, such as anastrozole. 3.Therapeutic potential of Omega-3 Fatty Acids Supplementation Aside from pharmacological interventions, dietary intervention is worth exploring, specifically in supplementing and enhancing well-tested cancer therapies. Omega-3 FAs, such as eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively), are the nutrients heavily studied for their potential use in this approach. Remarkably, consumption of omega-3 FAs is associated in numerous studies with the decreased risk of multiple cancer types, including gynaecological cancers, accomplished primarily through their anti-inflammatory action. The use of omega-3 FAs to inhibit the progression of gynaecological cancer may be more beneficial in obese patients, as rats given high-fat diets had lower NF-κB mRNA levels and DNA binding than control-diet rats when both were treated with omega-3 FAs. Other than their anti-inflammatory properties, omega-3 FAs could also retard the growth of gynaecological cancers by interfering with the action of oestradiol, directly or indirectly, in dysregulating FA metabolism in these cancers. DHA reportedly abrogated the FASN upregulation and pAkt/Akt increase in MCF7 induced by oestradiol while also inhibiting oestradiolinduced promotion of the SREBP isoform SREBP-1 protein expression, and these abrogations were further enhanced upon adding the Akt inhibitor LY294002. The pro-tumorigenic impact of oestradiol on FASN in breast cancer could, therefore, be significantly inhibited with DHA supplementation in combination with Aktinhibiting agents. Intake of omega-3 FAs, however, should be accompanied with caution, as excess consumption is linked to several adverse effects, including the increased risk of prostate cancer, another hormone-responsive cancer type, which may also imply the elevated risk of gynaecological cancers. Therefore, optimising the omega-3 FAs intake of each patient is paramount to avoid such side effects when administering omega-3 FAs, alone or with established cancer treatments, to fully take advantage of the tremendous therapeutic potential of omega-3 FAs. In summary, several promising drugs rectifying dysregulated lipid metabolism are now at various stages of development. These can be combined with oestradiol pathway-targeting chemotherapeutic agents to enhance the potency of or circumvent cancer resistance against these agents. The therapeutic use of omega-3 FAs is a significant milestone in applying dietary interventions as an adjunct to well-established regimes in treating gynaecological cancers. Reference: 1. This entry is adapted from https://doi. org/10.3390/metabo12040350 2. Mozihim AK, Chung I, Said NABM, Abd Jamil AH. Reprogramming of Fatty Acid Metabolism in Gynaecological Cancers: Is There a Role for Oestradiol? Metabolites. 2022; 12(4):350. L Figure 1 Overview of the various aspects of fatty acid metabolism and their dysregulation in gynaecological cancers. 20 / THE PANACEA / VOLUME 2 2023 RESEARCH HIGHLIGHTS

Exploring the role of the cholesterogenic gene, FDFT1 in obesity Intan Syakirah Mohd Ramdzan, Amira Hajirah Abd Jamil, Nur Akmarina Mohd Said* Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya Correspondence to*- [email protected] Obesity is characterized by having a body mass index (BMI) of ≥30 kg/m2 or more significant due to abnormal accumulation of fat. Malaysia, with an obesity prevalence of 19.7% - has topped the other Southeast Asian countries (Ministry of Health [MOH], 2019). Persistent non-optimal dietary practices and a sedentary lifestyle have contributed mainly to this. High-fat diet (HFD) has been associated with elevated BMI and, consequently, increased risk of obesity due to storing excess fat in the body. Moreover, the habit of repeatedly heating cooking oil for deep-frying foods among Malaysians have been shown to generate lipid peroxidation products, enhancing the risk of obesity (Adriana, Saliza, Mohd Redzwan, 2018; MOH, 2020). Obesity has always been associated with the disruption of cholesterol homeostasis that is influenced by cholesterol ingestion, absorption, synthesis, and excretion (Mc Auley, 2020). Cholesterol can either be from the dietary source or intracellularly synthesizedmainly by the liver. Obesity disrupts cholesterol homeostasis by increasing the rate of cholesterol synthesis in the liver, causing hypercholesterolemia i.e., increased low-density lipoprotein (LDL) but low high-density lipoprotein (HDL) (Ha & Lee, 2020; Mc Auley, 2020). Currently, studies only revealed that liver hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme in the cholesterol biosynthesis pathway, increases in obese subjects compared to the controls (Mc Auley, 2020). However, no extensive studies have been conducted on other liver cholesterol synthesis genes thus far. The farnesyl-diphosphate farnesyltransferase 1 (FDFT1) gene is pivotal in regulating cholesterol synthesis (Apryatin et al., 2019; Yasar et al., 2018). FDFT1 mainly works downstream of the cholesterol biogenesis pathway and is responsible for encoding the enzyme squalene synthase (SQS) to convert farnesyl pyrophosphate (FPP) to squalene, the first specific precursor for cholesterol synthesis (Figure 1) (Ha & Lee, 2020). To gain preliminary insight onto the impact of obesity on other components of the cholesterol metabolism pathway in the liver, we investigated the expression of liver FDFT1 in an obese rodent model. The obese rodent models were generated (Ethics approval number: 2018-211108/ PHARM/R/AHAJ) and divided into 3 groups (each group n=5), with the control group being chow-fed animals. The two obese groups are HFD complemented with 15 % (w/w) fresh palm oil (FPO) and HFD completed with 15% (w/w) ten times reheated palm oil (RPO). At the end of 6 weeks of feeding, adiposity index - a measure of epididymal fat pad weight to body weight ratio showed a significant increase in obese groups compared to the controls (p<0.05) - indicating that the HFD successfully induced obesity in the models. While the total cholesterol (TC) across the groups showed no significant difference, triglycerides (TG) level was significantly increased in the obese, diabetic HFD-fed rats compared to chow-fed diet rats. The liver of the controls and obese rodents were harvested, and FDFT1 gene expression in the hepatocytes was measured using real-time quantitative polymerase chain reaction. FDFT1 gene expression was significantly decreased in the RPO group compared to the control group by 90% (p<0.05). Although insignificant, the FDFT1 gene expression showed a decreasing trend between control and FPO groups and between FPO and RPO groups (Figure 2). The results preliminarily suggest that obesity is negatively correlated with FDFT1 expression. A negative feedback mechanism has been suggested to regulate overproduced cholesterol by the liver, where suppression of intracellular cholesterol synthesis by the liver takes place to establish the normal cholesterol level. The cholesterol synthesis genes may be affected by this regulatory mechanism. Therefore, we Figure 1. Flow chart illustrating cholesterol biogenesis pathway7. Figure 2. Relative FDFT1 gene expression. The FDFT1 gene expression of control, FPO and RPO groups were expressed as mean ± SEM (n=5). *p < 0.05 vs. control. FPO: diabetic rats fed fresh palm oil, RPO: diabetic rats fed reheated palm oil. deem it as one of the possibilities to justify the behaviour of FDFT1 gene expression in obese conditions. (Okazaki et al., 2006). Obesity is also linked with oxidative stress via enhanced production of reactive oxygen species (ROS) (Fernández-Sánchez, 2011). A significant increase in epididymal fat pad weight and the epididymal fat pad weight and body weight ratio in obese models compared to THE PANACEA / VOLUME 2 2023 / 21 RESEARCH HIGHLIGHTS

the controls enhances visceral fat stores (Fujita, Nishizawa, Funahashi, Shimomura, & Shimabukuro, 2006). Adipocytes have been shown to generate more ROS that will influence intracellular cholesterol homeostasis by upregulating the hepatic HMGCR activity advancing cholesterol synthesis in obese conditions (Fujita et al., 2006; Pallottini et al., 2006). However, how obese-induced ROS production affects liver FDFT1 expression is yet to be described. In conclusion, our study demonstrates that obesity negatively correlates with liver FDFT1 gene expression in our rodent models. However, the role of liver FDFT1 in cholesterol metabolism, specifically in obese conditions, is yet to be known due to several limitations in this study. Firstly, our models were obese diabetic rats with one group fed with RPO. Adding T2DM and ROS elements makes it hard to dissect the true effect of obesity on liver FDFT1 gene expression as T2DM and ROS could serve as the cofactors. In addition, the small sample size also mitigates the significance of our study, and we lack complementary tests or data to support our hypothesis – including the cholesterol profile analysis. References 1. A. A. Aziz, S.M. Elias and M. R. Sabran, Journal of Medicine and Health Science 14 (2), 37-44 (2018). Online learning and public health at higher education institutions in low- and middle-income countries: A catalyst or turn-off? Izyan A. Wahab PhDª*, Azyyati Mohd Suhaimi PhDᵇ, Nor Hayati Abu Samah PhDc ª Faculty of Pharmacy, University of Malaya, 50603 Kuala Lumpur, Malaysia b Faculty of Pharmacy, Universiti Sultan Zainal Abidin, 22200 Terengganu, Malaysia c Faculty of Pharmacy, Universiti Teknologi MARA, Selangor Branch, Puncak Alam Campus, 42300 Puncak Alam, Selangor, Malaysia **Correspondence to * - [email protected] 2. M. T. Mc Auley, Nutrition Research Reviews 33(1), 121–133 (2020). 3. S. A. Apryatin, N. V. Trusov, A. Y. Gorbachev, V. A. Naumov, A. S. Balakina, K. V. Mzhel’skaya and I. V. Gmoshinski, Biochemistry 84 (9), 1093–1106. (2019). 4. A.Fernández-Sánchez, E. MadrigalSantillán, M.Bautista, J. Esquivel-Soto, A. Morales-González, C. Esquivel-Chirino, I. Durante-Montiel, G. Sánchez-Rivera, C. Valadez-Vega and J. A. Morales-González International Journal of Molecular Sciences, 12 (5), 3117–3132. (2011). 5. V.Pallottini, C. Martini, A. M. Bassi, P. Romano, G. Nanni, and A. Trentalance. Journal of Hepatology, 44, 368–374. (2006). 6. N. T. Ha and C. H. Lee. Cells, 9 (11), 2352. (2020). L Introduction As the stakeholders embrace graduands who graduated two years after the first COVID-19 outbreak worldwide, there remains the question of whether the pace of education institutions for future outbreak preparedness and response is at its acceleration as it should be. For example, as an employer, can I trust healthcare graduates’ competence skills learned in 2021 and 2022 to be in my team and provide optimal patient care? As a student, did I learn and gain sufficient skills during the two-year pandemic and be ready to work? As an educator, am I doing justice to students, employers, parents and scholar funders to produce the same quality of pre-pandemic graduands? Do these questions even matter to public health? Online learning in Malaysia began in the late 1990s, whereby the physical teaching and learning (TnL) instructional contents were digitalised during the early phase.1 Subsequently, blended learning was implemented in many higher education institutions to complement the physical face-to-face TnL activities by integrating technology and digital media. Significant efforts have been undertaken since then to equip and enhance the higher education facilities in expediting the application of online learning. The government’s commitment to online learning was again highlighted in the Malaysia Education Blueprint 2015–2025,2 aiming for 70% of educational programs to adopt blended learning models. Until now, however, many academicians are apprehensive about blended TnL. Not surprisingly, their concerns are valid as the internet coverage and speed are not yet optimal for online learning implementation at full length in this country. Even though internet access has been demonstrated to increase up to 90%,3 its penetration in underdeveloped and rural areas is still limited. There was a massive variation in internet speed among the states, ranging from 91.8 Mbps download speed in the more developed region to as low as 36.6 Mbps in the developing states.4 There was also an expectation of a low number of students’ engagement during online learning,5 complicated by the inexperienced educators at their wit’s end for not being fully trained to teach online.6 It is important to note that the coronavirus outbreak may not be the last pandemic in our lifetime with menacing global impacts. The high mutation rate of coronavirus, growing population immunity and increased immunocompromised populations allow the emergence of new variants. Without robust quality of higher education delivery, future workforce and leaders in healthcare may not be able to safeguard public health. The current generation of students has the right to access high-quality education efficiently. The two-year COVID-19 crisis has unveiled the potential and real problems that may have been previously barricaded with loose pre-pandemic prevention strategies. At the same time, it widens the gaps of inequalities in higher education in many parts of the world, especially in developing countries with resourcelimited settings. Maintaining mental health survival may be more difficult in future pandemic outbreaks if a similar response from higher education for the last pandemic persists. The hazardous outcome of selfisolation is evident when many students believed they were under-prepared for their professions when their clinical internship training became affected.7 Pre-recorded lectures were viewed less significantly by the disadvantaged students as opposed to the conventional face-to-face approaches.8 In essence, many were concerned about their future employment and thus risked succumbing to the pressure with consequent degrading general well-being.9 Furthermore, mental health among young adults and women 22 / THE PANACEA / VOLUME 2 2023 RESEARCH HIGHLIGHTS

is disproportionally affected during this period, where South Asian and lowmiddle-income countries have the highest percentage of depression cases.10 Since the pandemic, there has also been an increase in faculty members considering leaving their jobs or reducing employment time, especially those with children.11 It is apparent that these populations’ social welfare system was not operating optimally during this challenging period, compounded by the poorly designed support system from higher education to deliver online TnL to ensure learning continuity. We have seen a continued fast pace of changes in the authorities’ decisions, instructions, rules, and regulations where such alterations have primarily impacted the executioners; in this case, the academicians and students were expected to adapt swiftly to the new requirements. As a result, mental fatigue creeps in, and the root cause is frequently disregarded with other non-work or study matters for survival during the global emergency. The higher education providers introduced several initiatives to minimise the negative disruption and ensure the continuity of TnL activities. For instance, some universities had either reduced or waived tuition fees, particularly for students who were financially affected by the crisis. Others provided technical assistance for online learning, such as free internet access and learning devices. In addition, alternative assessments were implemented for students to undertake the evaluation remotely to replace their final examinations. However, these initiatives were partial and reactive measures in response to the lockdown. Nonetheless, such assessments were not even conclusive in evaluating similar competence pre-pandemic. Although other new digital technology approaches were promptly reinforced to mimic the final examination process, caution should always be exercised to protect academic integrity and minimise online cheating. The methods can be counterproductive if operated without considering the requirements for efficient use of online learning technologies such as internet speed variation, servers, specification tools and software availability.12 With substandard preparations, educators and students are thrown at the deep end to lose interest in engaging in online TnL. Eventually, online learning can be inadvertently perceived as a turn-off tool. Developed countries are more amenable to switching from the traditional to online TnL with technological resources to ensure the continuity of higher education for future healthcare workforce and leaders. The percentage of internet users exceeds 90% in developed countries compared with only 47% in developing countries.13 The responsibility of maintaining public health should be within the vicinity of household communities at large and through higher education institutions. Careful deliberation and strategies are warranted to safeguard students and employees from anxiety regarding their tertiary education consumption and workplace. This Opinion identifies available opportunities for online learning as a catalyst in the postpandemic era toward sustaining robust and high-quality higher education delivery systems in low- and middle-income countries. Key opportunities to be caught post-pandemic Returning to face-to-face TnL and leaving behind online learning is well anticipated by all students and academicians. After being pushed to the brink of self-quarantine during the global crisis, the prospect of having more meaningful communication and a tangible environment in the endemic phase allows them to gradually restore the normal education system. However, this ‘new normal’ era necessitates viable acute and intermediate goals (Figure) to strengthen the digital higher education blueprint during the pandemic or national crisis period. In low- and middle-income countries, building human capital must be addressed strategically through enhanced collaboration and communication skills, improved infrastructures, idyllic environments and revised online TnL contents. Furthermore, higher institutions in these countries must be able to move beyond the conventional ways of handling TnL. People must surpass the old protocol-driven culture, avoid delegating unfathomable instructions, allocate responsibilities, and acknowledge strengths and limitations respectfully to promote success in implementing online TnL. The final goal must benefit the education and healthcare fraternity, especially the students and academicians. For any new policies or projects, it is crucial to develop trust and accountability among colleagues in the workplace for smooth implementation. Trust is built on effective and timely communication skills. Leveraging trust can facilitate autonomy support and higher-level engagement, especially among new employees, by tapping into the energy, new ideas, and creative digital and technological tools for effective TnL. When all members of the community of practice are viewed as essential contributors to the organisation, it legitimises diverse members on the periphery. It encourages flexibility for the common goals: reliable background and information-sharing support highperformance employees in healthcare institutions during the COVID-19 pandemic. In the age of milliseconds of information propagated in media, employees and students must be provided with psychological safety and appropriate support responses. The information supply from institutions and management must be timely, transparent, and continuous to promote crème de la crème quality of work and study performance. On top of that, communication training is pertinent to all employees and employers for the success of online TnL. Some significant difficulties of communicating information through digital technologies are the absence of physical contact, facial expression, body language and voice tone for interpretation. Hence, conveying proper reasoning and reassurance are crucial to avoid ambiguity, misinformation, and contradiction when conducting online TnL. Several factors, including weak leadership, policy failures and lack of commitment, consensus and resources cause failure of sustainability in the higher education industry.14 It is crucial to secure inter-agencies collaboration, which can finance the development of educational infrastructures to create an ideal environment for practical and effective online TnL activities. Studies from the United Kingdom and Spain noted that the environmental and design elements of the infrastructures could affect students’ academic achievement.14,15 Infrastructure limitations faced by higher education institutions in conducting online TnL must be adequately Figure: The key strategies to achieve short-term and intermediate-term goals toward sustainability in higher education for online TnL post-pandemic THE PANACEA / VOLUME 2 2023 / 23 RESEARCH HIGHLIGHTS

discussed, and technical support must be made available for all parties involved. Ultimately, the online TnL implementation during the pandemic ought to be revisited, reflected, and assessed for improvement through a new breadth of digital curriculum review. Proficient integration of three learning domains (cognitive, affective and psychomotor) whilst conducting online TnL is achievable via constant human capacity training and progress for educators. In addition, the previously exercised continuous quality improvement for face-to-face TnL must consider various elements that may affect students’ ability to learn effectively. Engagement with the industrial players that provide remote services is beneficial as an alternative to students’ exposure to experiential learning. The digital economy is expected to contribute almost a quarter of Malaysia’s gross domestic product and create hundreds of thousands of job opportunities in 2025.16 However, experiential learning without digital service exposure is non-progressive, keeping the students and academicians from engaging with real-world scenarios. These key actions should be tackled urgently and resolved within the first two years post-pandemic. In the intermediate post-pandemic period strategy to face another crisis, strategic logistic measures to ensure the continuity of online TnL must be identified, improved, and simulated in the higher education communities (Figure). In the acute phase of urgent crises, fear, confusion, and anxiety commonly occur during the fight or flight response. Without clear and known designated evacuation or logistic processes, online TnL can be interrupted, and disadvantaged students are potentially left behind. Like thefire drill exercises reinforced by the occupational safety and health and environment unit in any institution, crisis training must be mandatory for students and employees to identify alternative safe travel routes and spaces to continue online TnL. Finally, identifying and maintaining collaboration with digital and technology industry players are important not only for investment in building human capacity but also to ensure that the academic programs are relevant, current, and meeting the demands of employers and communities. Higher education institutions are optimally positioned to undertake virtual and augmented reality research to complement online TnL. Studies have shown that virtual augmented reality technology can enhance students’ experiential learning, allowing them to attempt exercises as often as possible according to their learning pace.17 Its use had previously been associated with enhanced educational outcomes by allowing students to engage in laboratory experiments that are difficult to conduct in the real world.18 Additionally, an augmented reality-based clerkship program can allow healthcare students to engage in authentic explorations in the hospital or clinical setting.19,20 Conclusion Addressing current issues experienced by higher education communities and institutions with compassion can offer sensible planning for online TnL activities in low- and middle-income countries. The pandemic’s toll on the students’ and academicians’ mental health must be addressed adequately. Tragedies and casualties caused by the COVID-19 pandemic should educate us to strive for more systematic planning where human welfare, values and dignity must be at its core. Strategies to implement effective online TnL will vary between countries depending on their cultures, needs and available resources. Recognition of the strengths and limitations of the institutions should expedite cooperation and partnership with external linkages for the sake of public health’s well-being. References 1. Haron H, et al. The adoption of blended learning among Malaysian academicians. Procedia - Soc Behav Sci 2012; 67: 175–81. 2. Ministry of Education Malaysia. Malaysia Education Blueprint 2015-2025 (Higher Education). Putrajaya, Malaysia, 2015. 3. Department of Statistics Malaysia. ICT use and access by individuals and households survey report, Malaysia 2021. Malaysia, 2022 https://www.dosm.gov.my/portal-main/ home. 4. Gómez MFV. Exploring internet performance in Malaysia. 2020. 5. She L, et al. Online learning satisfaction during COVID-19 pandemic among Chinese university students: The serial mediation model. Front Psychol 2021; 12. DOI:10.3389/ fpsyg.2021.743936. 6. Selvanathan M, et al. Students learning experiences during COVID-19: Work from home period in Malaysian Higher Learning Institutions. Teach Public Adm 2020: 014473942097790. 7. Zhang W, et al. Impact of postgraduate student internships during the COVID-19 pandemic in China. Front Psychol 2022; 12. DOI:10.3389/fpsyg.2021.790640. 8. Summers R, et al. The impact of disadvantage on higher education engagement during different delivery modes: a pre- versus peri-pandemic comparison of learning analytics data. Assess Eval High Educ 2022: 1–11. 9. Plakhotnik MS, et al. The perceived impact of COVID-19 on student well-being and the mediating role of the university support: Evidence from France, Germany, Russia, and the UK. Front Psychol 2021; 12. DOI:10.3389/fpsyg.2021.642689. 10. Hossain MM, et al. Prevalence of anxiety and depression in South Asia during COVID-19: A systematic review and meta-analysis. Heliyon 2021; 7: e06677. 11. Matulevicius SA, et al. Academic medicine faculty perceptions of work-life balance before and since the COVID-19 pandemic. JAMA Netw Open 2021; 4: e2113539. 12. Almaiah MA, et al. Exploring the critical challenges and factors influencing the E-learning system usage during COVID-19 pandemic. Educ Inf Technol 2020; 25: 5261–80. 13. International Telecommunication Union, United Nations Office of the High Representative for the Least Developed Countries, Landlocked Developing Countries and Small Island Developing States. Connectivity in the least developed countries: Status report 2021. 14. Barrett P, Treves A, Shmis T, Ambasz D, Ustinova M. The impact of school infrastructure on learning: A synthesis of the evidence. Washington: World Bank Publications, 2019. 15. López-Chao V, et al. Architectural indoor analysis: A holistic approach to understand the relation of higher education classrooms and academic performance. Sustainability 2019; 11: 6558. 16. Ahmad A. Malaysia’s digital economy to contribute 22.6% to GDP, create half a million jobs by 2025. Bernama. 2022; 17. Radianti J, et al. A systematic review of immersive virtual reality applications for higher education: Design elements, lessons learned, and research agenda. Comput Educ 2020; 147: 103778. 18. Rojas-Contreras M and Ruiz-Bautista LE. Online laboratories supported with virtual reality for higher education. J Phys Conf Ser 2020; 1708: 12036. 19. Dhar P, et al. Augmented reality in medical education: students’ experiences and learning outcomes. Med Educ Online 2021; 26: 1953953. 20. Bellamy E, et al. Opportunities for augmented reality in clinical simulation education. Nurs. Times. 2022. L 24 / THE PANACEA / VOLUME 2 2023 RESEARCH HIGHLIGHTS

T he Faculty of Pharmacy Postgraduate Society was established on October 2021 with Universiti Malaya. The aim of our Society is to unite all the postgraduate students at our faculty and to share, collaborate and communicate about today’s world pharmaceutical applications in research and academia. In our society, we currently have 29 Ph.D. and 19 Masters students with unique and diverse backgrounds consisting of local and international students from countries. We have hosted and organized many events previously and some examples are SPSS, Systematic Literature Review, How-to write an award winning research proposal workshop and one of the most recent event we organized was the talk with Prof. Kevin. “How to approach postgraduate studies: an educational, psychological perspective” – My little note As soon as I learned that Professor Burgess would be giving a talk on “How to approach postgraduate studies: an educational, psychological perspective”, I quickly signed up to attend the event. To my surprise, I did not only take home many valuable tips for my postgraduate career but also for my personal journey. Professor Burgess lit up the room with silly jokes and a bright smile. He had our attention throughout the whole talk, keeping us engaged and welcoming all sorts of questions. The talk was about the crucial planning steps in a PhD programme, including highlighting the beauty of a scientific method (I know, how mindblowing!); how to plan an experiment. He broke down the talk into two parts: Planning a PhD and getting it done. The scientific method was, of course, applied in the planning section. The regular subjects include asking questions, establishing your hypothesis, designing your method, and performing your experiments. He shared the importance of these steps for us. The key to planning your PhD is to set realistic goals or milestones and specific aims always to measure progress and deliver results efficiently. Lastly, getting it done! He encouraged us to build a scientific second brain by providing tips on taking intelligent notes and organising and consolidating information and learning. This was my favourite part of the talk because he ignited and showed us a path to so many endless possibilities to pursue good habits and how to prioritise them. He also shared the creativity triangle with us! Learning, motivation and optimal performance! With all this new information I had absorbed, I felt so blessed and privileged to obtain the opportunity to join this talk. I want to immensely thank Professor Burgess for sharing his thoughts and experiences with us and pushing us out of our comfort zones. You are the best, Professor Burgess! Good luck with your YouTube videos; we are all rooting for you to be the next YouTube Star. The article is compiled by Annatasha Stephanie (PhD student). L Hands-on Pilot Scale Tablet Manufacturing Process: Powder to Pill At Faculty of Pharmacy, Universiti Malaya, we have solid pharmaceutical dosage design pilot plant equipped with advance manufacturing (High-shear mixer granulator, fluid bed dryer, blending machine and automated rotary tablet compression machine). We conduct WORKSHOP twice a year and it is open for all. For further details and service related info, contact: Dr. Syed Mahmood [[email protected]] (Manager Pilot Plant) Tel: +603 79675768 Additional services provided1. Trainings/hands-on (instruments) 2. Attachment for undergraduate students 3. tablet manufacturing for research studies and their testing POSTGRADUATE SOCIETY THE PANACEA / VOLUME 2 2023 / 25

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A pharmacist's SMILE is the best “ THERAPY “ THE PANACEA / VOLUME 2 2023 / 27

Contact Us Faculty of Pharmacy, Universiti Malaya Jln Profesor Diraja Ungku Aziz, 50603 Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur 03-7967 4909 Fax 03-7967 4964 (Pharmacy Publishing) | [email protected] Email (Faculty Administration) | [email protected] Email (Faculty ICT) | [email protected] pharmacyunimalaya umpharmacy ISSN 2948-3867 9772948386003 Printed by University of Malaya Press 50603 Kuala Lumpur