Lipid-Based Nanoparticles Liposomes VS. Lipid nanoparticles (LNPs)

Huateng Pharma https://us.huatengsci.com

Lipid-Based Nanoparticles: Liposomes VS.

Lipid nanoparticles (LNPs)

Lipid-based formulations have contributed to significant achievements in drug
development and the delivery of therapeutic biomolecules and genes. One
common misconception is that liposomes and LNPs are interchangeable
terms. They are similar ─ and both can be effective for drug delivery ─ but
are different in composition and function.

Lipid-Based Nanoparticles: Liposomes VS. Lipid nanoparticles (LNPs)

Lipid based nanoparticles, such as liposomes and solid lipid nanoparticles, can
be used to package drugs for topical, oral, intravenous or pulmonary routes of
administration. The first FDA-approved lipid-based drug formulation, Doxil®,
an antitumor antibiotic, was marketed in 1995. Since then, more than a dozen
additional FDA-approved therapeutics have been marketed for cancer, gene
therapy, antiviral vaccines, fungal diseases, analgesia and photodynamic
therapy. Hundreds more are in clinical trials and are even authorized for
emergency use - as in the case of Pfizer and the Moderna COVID-19 vaccine.
In fact, the greatest progress has been made in the area of nucleic acid
delivery, involving the encapsulation of short interfering RNA (siRNA),
microRNA (miRNA), short activating RNA (saRNA) or messenger RNA (mRNA)
in lipid nanoparticles for gene silencing or activation and protein production.
Liposomes were first described by the British hematologist Dr. Alec D
Bangham in 1964 (Published 1964), at the Babraham Institute in Cambridge.
Liposomes are self-assembled closed spherical structures composed of one or
more amphipathic phospholipid bilayers and an internal aqueous core, ranging

in size between 20 and ∼1000 nm. The core–shell nanostructure of liposomes

makes them suitable for loading both hydrophobic and hydrophilic molecules.
Normally, hydrophobic drugs are encapsulated in the lipophilic bilayers of the
shell, and hydrophilic drugs are to be entrapped in the aqueous phase of the
core, making liposomes a versatile drug delivery platform.
Lipid nanoparticles (LNPs) are very similar in basic physical structure of
liposomes. Their liposome-like structures especially geared towards
encapsulating a broad variety of nucleic acids (RNA and DNA) and as such,
they are the most popular non-viral gene delivery system.
There are three main differences between liposomes and lipid nanoparticles.

Huateng Pharma https://us.huatengsci.com

Figure 1. Liposomes VS. Lipid nanoparticles (LNPs)
1. The major difference between liposomes and lipid nanoparticles is
morphology. Liposomes are spherical vesicles with an aqueous internal cavity
enclosed by a lipid bilayer membrane, whereas lipid nanoparticles do not have
aqueous internal cavities. In contrast, lipid nanoparticles form multilayer cores
dispersed between lipid layers due to the electrostatic complexation of cationic
phospholipids and negatively charged nucleic acid substances.

2. In terms of composition, the main components of LNPs and liposomes are
roughly the same, both containing lipids and cholesterol, except that ionizable
lipids must be present in the lipids used in lipid nanoparticles, while liposomes
do not have strict requirements on the type of lipids. However, there is a big
difference between liposomes and lipid nanoparticles in terms of the ratio of
each component, especially the amount of cholesterol. Take the classic
liposomal product DOXIL as an example, HSPC:CHOL:DSPE-PEG2000 =
3:1:1. In contrast, the components of the two marketed mRNA COVID-19
vaccines contain 42.7% (Pfizer/BioNTech) and 38.5% (Moderna) of
cholesterol, respectively, which are significantly higher than the cholesterol
content in liposomes.

3. In terms of production processes, liposomes and lipid nanoparticles are
different in upstream manufacturing processes, but are almost identical in
downstream manufacturing processes. The conventional liposome preparation
process starts with the formation of crude liposomes from the lipid and
aqueous phases, and then the particle size is controlled within a certain range

Huateng Pharma https://us.huatengsci.com

by homogenization or extrusion process; while lipid nanoparticles are rapidly
mixed with lipid ethanol solution and aqueous nucleic acid acidic solution using
a microfluidic mixing system with connectors that can control the particle size
during the mixing and collision of the two phases. The buffer replacement
process downstream of liposomes and lipid nanoparticles is almost the same,
both use Tangential Flow Filtration (TFF) technology for buffer replacement or
purification, and finally filter through the terminal 0.22μm filter membrane for
sterilization.

Figure 2. Liposomes and Lipid nanoparticles manufacturing process

Advantages of Lipid-Based Nanoparticles

Lipid-based nanoparticles have received significant attention in drug discovery
and delivery. These nanoparticles can transport hydrophobic and hydrophilic
molecules to enhance the bioavailability of therapeutic compounds by
controlling solubility, permeability, absorption, distribution, and metabolism.
In addition, these nanoparticles show very low or no toxicity and increase the
duration of drug action by extending the half-life and controlling drug release.

Lipid nanosystems can include chemical modifications to avoid detection by
the immune system (gangliosides or polyethylene glycol (PEG)) or to improve
therapeutic index. For example, PEG covalently linked to liposomes can
reduce immunogenicity and antigenicity, protecting them from the training of
the receptor's macrophage system to destroy foreign substances. The addition
of PEG can also alter physicochemical properties, reduce renal clearance,
prolong circulation time, and reduce the frequency of dosing.

Moreover, they can be prepared as pH-sensitive formulations to facilitate drug
release in an acidic environment, or they can be associated with antibodies
that recognize tumor cells or their receptors, such as folic acid (FoA).
Nanodrugs can also be used in combination with other therapeutic strategies
to improve the response of patients.

Huateng Pharma https://us.huatengsci.com

Conclusion

Lipid-based nanoparticles designed for drug delivery show great potential in
overcoming the limitations of conventionally formulated drugs, enhancing their
therapeutic efficacy.These nanoparticles hold great promise in genetic
medicine where gene editing, vaccine development, immuno-oncology, and
other genetic therapies rely on the ability to efficiently deliver nucleic acids into
cells.

As a leading supplier of PEG lipids, Huateng Pharma provides a wide array
of PEG lipids to our clients worldwide, such as PEG-DSPE, PEG-DMG, etc.
Huateng Pharma also provides fast speed custom synthesis of novel PEG
lipids to empower your advanced research. Please email at
[email protected].

References:
1. Daraee H, Etemadi A, Kouhi M, Alimirzalu S, Akbarzadeh A. Application of
liposomes in medicine and drug delivery. Artif Cells Nanomed Biotechnol.
2016;44(1):381-391. doi:10.3109/21691401.2014.953633
2. LNPs vs. Conventional Liposomes: A Short Review Of Core Structural And
Manufacturing Differences. Bioprocess Online
3. García-Pinel B, Porras-Alcalá C, Ortega-Rodríguez A, Sarabia F, Prados J,
Melguizo C, López-Romero JM. Lipid-Based Nanoparticles: Application and
Recent Advances in Cancer Treatment. Nanomaterials (Basel). 2019 Apr
19;9(4):638. doi: 10.3390/nano9040638. PMID: 31010180; PMCID:
PMC6523119.

Related Articles:
Lipid Nanoparticles (LNP) for mRNA Drug Delivery
mRNA Technology: How To Achieve Targeted Delivery to Organs, Cells,
Tumors?
5 Types of COVID-19 Vaccines