Pentacyclic triterpenes modulate liposome membrane fluidity and permeability depending on membrane cholesterol content

Abstract

Since the membrane-related processes represent an integral part of the biological activities of drugs, their effect on the membrane dynamics is actually considered. In this study, we investigated the effect of pentacyclic triterpenes (TTPs), oleanolic acid (OA) and erythrodiol (ER), on the fluidity and permeability of liposomes membranes differing by their cholesterol content. All liposomes were prepared by reverse phase evaporation technique (REV). Spin-labeled liposomes exposed or not to TTPs were used for fluidity studies by using 5- and 16-doxyl stearic acids (DSA). TTPs-loaded liposomes (phospholipid:cholesterol of 1:1), and preformed vesicles exposed to TTPs were used for permeability studies by monitoring the release of sulforhodamine B (SRB) at 37 °C. The apparent release constants of SRB were determined by Higuchi model based on a biphasic curve shape (0–10 h; 10–48 h). TTPs-loaded liposomes were characterized for their size and homogeneity. Results showed that ER increased the membrane fluidity at the upper region of the membrane while the both TTPs produced a condensing effect at the deeper region of the membrane. The membrane composition was a critical parameter modulating the effect of TTPs on the membrane permeability. Also, this study consolidated the fact that a fluidizing membrane agent is not necessarily a permeabilizing-membrane compound.