RESEARCH & DEVELOPMENT
‘Smectic Mesophases’, and ‘Liposomes’. The latter, a more user-friendly name representing their structure, comprised of the Greek words ‘lipos’ for fat and ‘soma’ for body. Eventually, the more user-friendly name ‘liposomes’, proposed by the late Gerald Weissmann, dominated internationally and became part of book titles and a Journal, biotech industries, conferences and products, including anticancer and anti-microbial agents, and Dior perfumes. More recently, the term ‘Lipid Nanoparticles’ was introduced, a name that does not seem to add significantly to its meaning as liposomes can also be of nano size. Work by Gregoriadis and Ryman during 1970-1972 established liposomes as a promising drug delivery system. Subsequently, work by the author and colleagues, notably the late Anthony Allison at the Clinical Research Centre in Harrow, London, demonstrated the immunological adjuvant action of liposomes using tetanus toxoid as a model antigen. The liposomal system was eventually adopted by a myriad of workers with dozens of enzymes, drugs and antigens and many other actives
entrapped in liposomes of varying sizes, lipid composition, surface charge, ability to accommodate water soluble or lipid soluble materials and, if needed, provide a pegylated vesicle surface, thus leading to the production of liposomes for multiple uses. These included a variety of therapeutics for cancer, anti-microbial therapy, lysosomal storage diseases (eg. Gaucher’s disease), and conventional or genetic vaccines. A great variety of liposome-based products have been already marketed. Liposomes and Nucleic Acids
It was predicted early in the use of liposomes as a drug delivery system that the system would play a significant role in employing the use of nucleic acids, including mRNA delivery. However, a variety of problems associated with the stability of liposomes in the circulating blood, their rapid removal from the blood circulation, and the limited extent by which drugs could be accommodated within liposomes had to be first
resolved. It was, for instance, essential that liposomes were rendered stable in blood. It was established that liposomes were destabilised because of the removal of phospholipid molecules from the liposomal bilayers and the creation of leaky pores through the action of plasma high density lipoproteins. Removal of phospholipid from the bilayers was prevented by the incorporation into the structure of liposomes of cholesterol that was equimolar to the phospholipid and by the choice of a high melting phospholipid, eg. distearoyl phosphatidyl choline. High entrapment values of nucleic acids were achieved by inserting cationic lipids into the bilayers of liposomes which would then bind to the anionic nucleic acid thus leading to high values of nucleic acid (eg. mRNA) association with or entrapment into liposomes. It was shown that plasmid DNA (pRc/CMV HBS coding for the hepatitis B surface antigen (S region), entrapped in liposomes of a composition identical to that just described, and injected through a variety of routes, not only expressed itself to produce the protein antigen, humoral and cell-mediated immune responses to the produced antigen were far greater than when the free plasmid was injected. Experiments with a plasmid coding for a variety of other antigens, gave similar results.
www.pharmafocusasia.com
39