- 1965: Alec Bangham described the first closed bilayer phospholipid systems, first called "bangosomes," now called liposomes.
- 1971: Gregory Gregoriadis proposed the use of liposomes for drug delivery.
- Problems with the first generation liposomes:
-In order to “tighten” the membrane and thus prevent leakage, cholesterol and sphingomyelin were added to the bilayer and the bilayer was switched from fluid-phase to solid phase.
2.) Rapid phagocytosis by the liver and spleen reduced distribution capabilities and increased toxicity.
-The addition of cholesterol and sphingomyelin to the bilayer increased the circulation half-lives of liposomes, forming “stealth liposomes” that were less likely to be phagocytized.
-Liposomes have been further stabilized by grafting polyethylene glycol (PEG) onto their membranes. These PEGylated liposomes are nearly dosage-independent, as their long circulation time prevents the previously toxic rapid phagocytic uptake.
3.) Passive delivery only worked for certain drugs; other drugs requried receptor-mediated endocytosis.
-Some drugs can simply be released by the liposome near their target and they will passively diffuse across the cell's membrane.
-Antibodies can now be added to PEGylated liposomes in order to allow for receptor-mediated endocytosis of liposomal contents.
4.) It was difficult to trigger the release of liposomal contents.
-Current triggers may be remote, like heat or light, or may be intrinsic, like enzymes or a change in pH.
*Remote triggering of hyperthermia to tumor cells has been shown to result in a four-fold increase in drug release.
*Designing liposomes to release their contents at a certain pH level has proven to increase membrane fusion and thus drug release to an intracellular target.
Allen, T. M. and Cullis, P. R. 2013. Liposomal drug delivery systems: from concept to clinical applications. Advanced Drug Delivery Reviews. Vol 65, No. 1: 36-48.
Lian, T. and Ho, R.J. 2001. Trends and developments in lioposomal delivery systems. Journal of Pharmaceutical Sciences. Vol 90, No. 6: 667-680.
Lian, T. and Ho, R.J. 2001. Trends and developments in lioposomal delivery systems. Journal of Pharmaceutical Sciences. Vol 90, No. 6: 667-680.