USE OF POLYOXYETHYLENE-LIPID CONJUGATES AS LONG-CIRCULATING CARRIERS FOR DELIVERY OF THERAPEUTIC AND DIAGNOSTIC AGENTS

The utilization of micelle forming block-copolymers as long-circulating drug carriers for sparingly soluble or amphiphilic drugs or diagnostic agents is reviewed with the emphasis on the use of phosphatidylethanolamine-polyethyleneoxide (PE-PEO) conjugates as structural amphiphilic polymers for formulation of polymeric micelles. PE-PEO conjugates spontaneously form particles with average diameter 10-30 nm depending on the molecular weight of PEO block and which are stable upon dilution at ambient temperature. Topoisomerase II inhibitor ellipticine was shown to be successfully incorporated into PE-PEO (5 kDa) conjugate micelles in vitro. Percutaneous lymphatic delivery of amphiphilic diagnostic agents incorporated into PE-PEO micelles was demonstrated using magnetic resonance imaging and gamma-scintigraphy. For water-soluble low molecular weight drugs one can expect hydrophobic prodrug approach to be most suitable for use with this drug delivery system.