Poly(Hpma)-coated liposomes demonstrate prolonged circulation in mice

Surface modification of liposomes with amphiphilic flexible polymers significantly prolongs their circulation time in blood and reduces uptake by cells of the reticuloendothelial system (RES). Several polymers have already been shown to provide steric protection to liposomes. Still more polymers are expected to serve this purpose, thus broadening the variability of properties of long-circulating liposomes. Poly[N-(2-hydroxypropyl)methacrylamide] (poly (HPMA)) seems to have some properties similar to polyethylene glycol (PEG), the most widely used polymer in liposome surface modification, including flexibility, hydrophilicity and low immunogenicity, which suggest that it may also function as an efficient steric protector of liposomes. Semitelechelic poly(HPMA) with single- or double-oleic acid hydrophobic terminus were synthesized and incorporated into the surface of liposomes composed of phosphatidylcholine and cholesterol. These poly(HPMA)-modified liposomes provided strong steric protection for liposomes, increasing their circulation time and decreasing liver accumulation in experimental mice. Poly(HPMA)-modified liposomes may become a useful addition to a family of long-circulating liposomes with potential to be used as a drug delivery system.