EFFECT OF COLLAGEN ON LIPOSOME PERMEABILITY

If liposomes are to be used as drug carriers, the encapsulating agents must not leak during storage. We showed previously that dispersion of liposomes (100% lecithin) in a collagen solution improves their chemi cal stability and decreases their permeability. This protective effect of collagen was studied further in a series of experiments: firstly, we tested the stability of various liposomes in the absence of collage n. When cholesterol or alpha-tocopherol was present in the bilayers of liposomes, both lipid peroxidation and liposome permeability decrease d. Peroxidation was responsible for 25% of the release of carboxyfluor escein, under our experimental conditions (20-degrees-C, liposomes sus pended in 300 mOsm/kg buffer); the release of the remaining 75% was pr obably due to simple passive diffusion of the molecules from the inter ior of the liposomes into the external media. Secondly, we examined th e stability of liposomes in the presence of collagen. In liposomes con taining 10 mol% of alpha-tocopherol, peroxidation was inhibited and no antioxidant effect of collagen was seen; however, permeability was de creased by 20% in presence of collagen. In liposomes containing 30 mol % cholesterol, the antioxidant effect of collagen and its effect on pe rmeability were similar to that in liposomes consisting of 100% lecith in. Furthermore, we studied the effect of surface charge. In neutral a nd positively and negatively charged liposomes, the antioxidant effect of collagen was similar; however, the stabilizing effect of collagen on permeability was completely suppressed in positively charged vesicl es but was 2-fold greater in negatively charged than in neutral liposo mes. The antioxidant effect of collagen thus led to only 20% decrease in liposome permeability, and 80% of the decrease was due to another m echanism, which may involve the electrostatic forces between collagen and phospholipids. The interaction between collagen and liposomes may thus involve the positive charges of this protein.