A novel approach to a controlled opening of liposomes

Abstract

A novel strategy is described for preparing pH-sensitive liposomes which releases the encapsulated drug in response to the change in pH of surrounding solution. The liposomes, composed of conventional zwitter-ionic egg yolk lecithin (EL), additionally contains a pH-sensitive "activator" (AMS), a derivative of lithocholic acid with anionic and cationic groups attached to the opposite ends of the steroid core. AMS changes its orientation in the liposomal membrane thus adapting to acidity/basicity of the outer solution. The rotation of AMS induces disordering of the membrane and a fast release of the bioactive cargo. In particular, 50-60 % of the encapsulated antitumor drug, doxorubicin and cisplatin, leaks from the liposomes within the first minute after acidification of the surrounding solution. Low-toxic EL-AMS liposomes, loaded with doxorubicin, show themselves active towards multidrug resistant cells. Fast-acting and low-toxic EL-AMS liposomes can be used in the design of smart liposomal containers in the drug delivery field.

Keywords: Cytotoxicity; Drug delivery; Drug release; Liposomes; Multidrug resistant cells; pH-sensitivity.