The stability of liposomes in vitro to pH, bile salts and pancreatic lipase.

If liposomes are to be effective as carriers for the oral administration of insulin they must be able to withstand passage through the stomach and small intestine. Multilamellar liposomes, some identical in composition to those used in reported in vivo studies on the uptake of orally administered insulin, were tested in vitro for their stability in the presence of bile salts, pancreatic lipase, and variations in pH. While low or high pH had little effect on most liposomes, 10 mM bile salts caused the release of over 80% of entrapped marker from all liposomes tested except those composed of distearoyl phosphatidylcholine/cholesterol and those composed of dipalmitoyl phosphatidylethanolamine/cholesterol/dicetylphosphate. However, the latter were unstable at low pH. The distearoyl phosphatidylcholine/cholesterol liposomes were also resistant to pancreatic lipase, and therefore may be suitable for use in the oral administration of therapeutic agents.