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Lipid-Based Nanoparticles: Liposomes VS. Lipid nanoparticles (LNPs)
Poster Title: Lipid-Based Nanoparticles: Liposomes VS. Lipid nanoparticles (LNPs)
Submitted on 08 Aug 2022
Author(s): Sally Zou
Affiliations: Hunan Huateng Pharmaceutical Co. Ltd.
Poster Views: 136
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Poster Information
Abstract: 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.

Liposomes VS. Lipid nanoparticles (LNPs)
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 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.

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
Summary: Liposomes and Lipid nanoparticles (LNPs) are similar ─ and both can be effective for drug delivery ─ but are different in composition and function.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.
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