Liposomes and PLGA nanoparticles as carriers for vaccines.

Liposome vaccine technology

Several applications of liposomes have been reported in the delivery of vaccine antigens. Liposomes can be used as carriers for vaccine delivery where antigens can be encapsulated in the core, embedded in the bilayer and/or adsorbed or engrafted to the outer Surface.

Although there are several formulations to obtain liposomes, cationic and fusogenic liposomes seems to be the most efficiency systems to deliver the vaccine antigens because their have a robust affinity for the negatively-charged biological membrane and they are able to be fused with this membrane to directly introduce the encapsulated material into the cytoplasm.

In addition to liposomes, virosomes have been used for several years in the development of new vaccines. Virosomes are structures similar to liposomes which have been decorated with viral proteins or viral envelopes acquiring viral functions.

In the last 20 years, liposome vaccine technology has matured and now several vaccines containing liposome-based adjuvants have been approved for human use or have reached late stages of clinical evaluation.

Some commercial products with this technology are Inflexal V (Influenza) or Epaxal (Hepatitis A)

 

PLGA nanoparticles vaccine technology

The specific advantages of using PLGA based nanoparticles in vaccines include their non-toxic and non-immunogenic properties for co-delivery of vaccine antigens and adjuvant. Besides, these nanoparticles have very good transfection efficiency to undergo internalization by the APCs for triggering the immune response in the body. In addition, the ability to manipulate the physico-chemical properties of these particles in order to tailor its rate of degradation and the subsequent release profile of the encapsulated molecules, is also an interesting advantage.

The efficiency of the transfection depends on the size and surface charge of PLGA nanoparticles. In general, PLGA nanoparticles (< 500 nm) are more effective than microparticles (> 2 um). Particles in the range of 20-200 nm are efficiently taken up by DCs via endocytosis or pinocytosis and facilitate the induction of cellular immune responses, whereas microparticles of 0.5–5 µm are taken up via phagocytosis or micropinocytosis.

Regarding the surface charge,  cationic PLGA particles are particularly effective for uptake by DCs and macrophages. The attraction between the positively charged particles and the negatively charged cell surface initiates efficient binding and facilitate particle internalization.

Entrapment of the antigen into the PLGA nanoparticle protects it from external environment but may lead to incomplete release, which could lead to a weak immune response; in contrast, adsorption may lead to high burst release, prematurely releasing the antigen from PLGA nanoparticle  before uptake by DCs, which can lead to deficient immune responses.  A combination of adsorbed and encapsulated antigen could be the best option.

Numerous antigens (proteins, peptides, lipopeptides, viruses or plasmid DNA) have been successfully formulated in PLGA particles.

 

 

Bibliography

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Mingyuan Li, Chunyang Du, Na Guo, Yuou Teng, Xin Meng, Hua Sun, Shuangshuang Li, Peng Yu, Hervé Galons. 2019. Composition design and medical application of liposomes. European Journal of Medicinal Chemistry. 164, 640-653.

Diana Felnerova, Jean-François Viret, Reinhard Glück, Christian Moser. 2004. Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs. Current Opinion in Biotechnology, 15, 518-529

Kaneda, Y. (2000). Virosomes: evolution of the liposome as a targeted drug delivery system. Advanced Drug Delivery Reviews, 43(2-3), 197–205

A.P. Silva, P.C. Soema, B.Slütter, F. Ossendorp and W. Jiskoot. 2016.
PLGA particulate delivery systems for subunit vaccines: Linking particle properties to immunogenicity. Human Vaccines & Immunotherapeutics, 12-4, 1056-1069

Samar Hamdy, Azita Haddadi, Ryan W. Hung, Afsaneh Lavasanifar. 2011. Targeting dendritic cells with nano-particulate PLGA cancer vaccine formulations. Advanced Drug Delivery Reviews. 63, 10-11, 943-955

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