Prolonged circulation time of doxorubicin-loaded liposomes coated with a modified polyvinyl alcohol after intravenous injection in rats

Abstract

The purpose of this study was to evaluate the functions of a modified polyvinyl alcohol (PVA-R), which has a hydrophobic moiety, as a coating material for liposomes to be loaded with the anticancer drug, doxorubicin. The size controlled liposomes (egg phosphatidylcholine: cholesterol=1:1 molar ratio) were prepared by the hydration method followed by extrusion. Drug encapsulation and surface modification with polymers (PVA and PVA-R) were carried out simultaneously using a modified pH gradient method. The existence of a thick polymer layer on the surface of the liposomes was confirmed by an increase in particle size and the amount of polymer on the liposomal surface, especially for the PVA-R-coated liposomes. The effects of polymer coating on the behavior of the liposomes in vivo were evaluated by measuring the circulation time and biodistribution of the drug after i.v. administration of the liposomal drug in rats. The PVA-R-coated liposomes showed a more prolonged circulating time for the drug with less uptake by the reticuloendothelial system after i.v. administration in rats, compared with non-coated liposomes. These results confirm that polymer possessing a hydrophobic anchor at its end, like PVA-R, is a suitable material for modifying the surface of doxorubicin-loaded liposomes to improve their stability in the circulating blood.