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.