Sunday, January 4, 2009

Liposome Stability

Almost every day we get a question about liposome stability. In this post we briefly explain the meaning of liposome stability.

Liposome stability is a complex issue. There are three types of liposome stability:

1) Physical stability
2) Chemical stability
3) Biological stability

Physical stability indicates the constancy of the size and the ratio of the lipid to the active compound such as drugs, DNA molecules, etc. The cationic liposomes can be stable at 4 degree centigrade (refrigerator) for a long period of time if they are properly sterilized.

Chemical instability primarily indicates hydrolysis and oxidation of lipids. Hydrolysis detaches the hydrophobic chains of ester bonds. Oxidation is more likely due to the presence of unsaturated chains. Adding antioxidants such as BHT to the liposome formulation can usually protect the lipids from oxidation.

Biological stability of liposomes is limited. Cationic liposomes in plasma are prone to aggregation and exhibit leakage. High density lipoproteins (HDLs) are responsible for destabilization of liposomes prior to interaction of liposomes with circulating phagocytic cells such as monocytes. The destabilization of liposomes is due to the lipid exchange between the liposomes and HDLs.

Industrial application of liposomes (e.g commercialization of liposomal drug formulations) requires an extensive shelf life studies. The expiration dating period or shelf-life of a drug product is defined as the time at which the average drug characteristic (e.g., potency) remains within an approved specification after manufacture. The United States Food and Drug Administration (FDA) requires that a shelf-life be indicated on the immediate container label of every drug product.

For more information about FDA guidelines see here:

http://www.fda.gov/RegulatoryInformation/Guidances/ucm128179.htm

The stability of many experimental liposome formulations that are made for research purposes are not tested. So it is better to use the experimental liposomal formulations as fresh as possible.