Stabilization of liposomes with collagen

Abstract

The potential use of liposomes as drug carriers is still limited by their poor stability under storage conditions and in biological media. As interactions between collagen and lipids have been demonstrated both in vitro and in vivo, we studied the stability of multilamellar liposomes at different temperatures in the presence and absence of type-1 collagen solution. The parallel release of 5(6)-carboxyfluorescein from liposomes (due to ‘spontaneous’ vesicle permeability or induced by detergent) and phospholipid peroxidation were measured as a function of time in the presence of different concentrations of collagen and of two other proteins: albumin and γ-globulin. In the presence of collagen, dose-dependent decreases in both ‘spontaneous’ liposome permeability and lipid peroxidation were observed. Albumin and γ-globulin had a similar antioxidant effect, but liposome permeability decreased to a lesser extent in the presence of these proteins than at the same concentration (0.8%) of collagen. Thus, the antioxidant effect of collagen cannot explain entirely its stabilizing potential, and collagen molecules would appear to have an additional, specific stabilizing effect on vesicle permeability. Furthermore, collagen as well as albumin and γ-globulin significantly decreased the deleterious effect of detergent on liposomes, probably through a direct interaction with the detergent. We conclude that dispersion of liposomes in a collagen solution may be a means of improving their chemical stability and decreasing their permeability.