Distinguishing between different types of nanocarriers can be confusing even for those who belong to the scientific community. Between the most popular lipid nanosystems, liposomes and lipid nanoparticles are often easily mistaken.

Furthermore, a basic understanding of both nanocarriers’ characteristics isn’t often enough when it comes to choosing between these two technologies for a specific drug delivery purpose. For this reason, the comparison of liposomes vs lipid nanoparticles often sparks debate among researchers.

In this article, we delve into the comparison of lipid nanoparticles vs liposomes, elucidating their respective characteristics and implications for drug delivery strategies.

 

Is a Liposome the Same as a Lipid Nanoparticle?

Although the terms “liposomes” and “lipid nanoparticles” are often mentioned interchangeably about lipid-based drug delivery systems, they are not synonymous. Each of these terminologies refers to a specific type of lipid nanocarrier, with structural differences often resulting in different applications.

The term “liposomes” refers to a specific type of nanocarrier characterized by a vesicular structure comprising one or more lipid bilayers encapsulating an aqueous core. They primarily comprise phospholipids and cholesterol and offer a proper environment for encapsulating hydrophilic and hydrophobic drugs within their aqueous core. They are highly versatile delivery systems that are used for a broad range of applications, including the delivery of small-molecule drugs, proteins, and vaccines [1].

However, in the last decades, there has been a notable evolution in the field of nanotechnology in response to the emergence of increasingly complex therapeutic molecules, like nucleic acids.

Many years of research have culminated in modern lipid nanoparticle (LNP) technology, defined as sub-micron particles containing ionizable cationic lipids in addition to other types of lipids and encapsulated nucleic acid. This technology is now the most clinically advanced non-viral gene delivery system as it now enables gene editing, protein replacement, and vaccines [2].

The composition of modern nucleic acid delivery systems derives from traditional liposomal systems for small-molecule therapeutics. Applying such systems to nucleic acid delivery revealed that the large size and high negative charge density of nucleic acids required additional lipid functionalities, including active encapsulation methods that liposomal lipid components did not provide. Iteratively improved formulation design, manufacturing processes, and ionizable lipid efficacy and tolerability resulted in the LNP formulation typically used today.

Therefore, when we mention LNP, we are referring only to formulations that contain these four lipids [3,4]: 

1. ionizable cationic lipids;
2. 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC);
3. cholesterol;
4. polyethylene glycol (PEG). 

 

These constituents facilitate monodisperse nanoparticle formation, improve nanoparticle stability, enable efficient nucleic acid encapsulation, aid cellular uptake, and promote endosomal escape of nucleic acid cargo. In particular, LNPs seem to be a versatile nucleic acid delivery platform that overcomes major hurdles in gene therapy, namely nucleic acid degradation and limited cellular uptake [5].

 

Drug Delivery Performance: Lipid Nanoparticles vs Liposomes

 

The debate about liposomes vs lipid nanoparticles highlights the need for a clear understanding of their strengths and weaknesses in drug delivery.

A fundamental point of divergence between lipid nanoparticles and liposomes lies in their structural organization. Lipid nanoparticles exhibit a more compact architecture, with a complex internal structure where ionizable lipids form an inverted micellar arrangement around the nucleic acid cargo. The structure can vary depending on the specific lipid composition and the type of cargo [2]. On the other hand, liposomes have a simpler bilayer structure, forming a spherical vesicle with an aqueous core. 

This structural compactness gives LNP higher colloidal stability compared to liposomes, which are prone to fusion and leakage. This stability ensures the integrity of the drug cargo during long-term storage and circulation in biological systems [6]. 

In addition, lipid nanoparticles have higher drug-loading capacities, allowing for the encapsulation of larger volumes of drugs, like nucleic acids, whose stability in liposomal nanocarriers is lower than that in lipid nanoparticles.

Lipid nanoparticles are nowadays the most popular non-viral system for gene delivery. Their prominence was shown by the Moderna and Pfizer COVID-19 vaccines, and more recently Moderna RSV vaccine, all of which employ lipid nanoparticles as mRNA carriers.

These nanocarriers are preferred to adeno-associated viruses (AAVs) as the latter can induce immune responses that limit repeated administration, present limited cargo capacity, and induce off-target genomic integration. Lipid nanoparticles show, instead, lower immunogenicity, allow repeated administration, and can efficiently encapsulate a wide range of cargoes.

In particular, DIVERSA has developed a technology that can efficiently deliver mRNA in vitro and in vivo and is comparable to LNPs Onpattro’s potency. By tailoring its components, DIVERSA’s technology can be also targeted to specific organs. 

This versatility can improve the pharmacological profile of a wide range of therapeutic molecules besides nucleic acids, such as small molecules, peptides, and proteins. Moreover, it offers a fluorescent option for efficient traceability.

DIVERSA also offers the possibility of testing such technology with our nanoparticle reagent, which is user-friendly and easily prepared without expensive equipment.

 

Do you want to know how to boost the potential of your therapeutical molecule? Contact us!

 

References

1. Allen, T.M.; Cullis, P.R. Liposomal Drug Delivery Systems: From Concept to Clinical Applications. Adv Drug Deliv Rev 2013, 65, 36–48, doi:10.1016/j.addr.2012.09.037.
2. Hald Albertsen, C.; Kulkarni, J.A.; Witzigmann, D.; Lind, M.; Petersson, K.; Simonsen, J.B. The Role of Lipid Components in Lipid Nanoparticles for Vaccines and Gene Therapy. Advanced Drug Delivery Reviews 2022, 188, 114416, doi:10.1016/j.addr.2022.114416.
3. Schoenmaker, L.; Witzigmann, D.; Kulkarni, J.A.; Verbeke, R.; Kersten, G.; Jiskoot, W.; Crommelin, D.J.A. mRNA-Lipid Nanoparticle COVID-19 Vaccines: Structure and Stability. International Journal of Pharmaceutics 2021, 601, 120586, doi:10.1016/j.ijpharm.2021.120586.
4. Kulkarni, J.A.; Cullis, P.R.; van der Meel, R. Lipid Nanoparticles Enabling Gene Therapies: From Concepts to Clinical Utility. Nucleic Acid Therapeutics 2018, 28, 146–157, doi:10.1089/nat.2018.0721.
5. Kulkarni, J.A.; Witzigmann, D.; Chen, S.; Cullis, P.R.; van der Meel, R. Lipid Nanoparticle Technology for Clinical Translation of siRNA Therapeutics. Acc. Chem. Res. 2019, 52, 2435–2444, doi:10.1021/acs.accounts.9b00368.
6. Kamiya, M.; Matsumoto, M.; Yamashita, K.; Izumi, T.; Kawaguchi, M.; Mizukami, S.; Tsurumaru, M.; Mukai, H.; Kawakami, S. Stability Study of mRNA-Lipid Nanoparticles Exposed to Various Conditions Based on the Evaluation between Physicochemical Properties and Their Relation with Protein Expression Ability. Pharmaceutics 2022, 14, 2357, doi:10.3390/pharmaceutics14112357.
7. Akinc, A.; Maier, M.A.; Manoharan, M.; Fitzgerald, K.; Jayaraman, M.; Barros, S.; Ansell, S.; Du, X.; Hope, M.J.; Madden, T.D.; et al. The Onpattro Story and the Clinical Translation of Nanomedicines Containing Nucleic Acid-Based Drugs. Nat Nanotechnol 2019, 14, 1084–1087, doi:10.1038/s41565-019-0591-y.