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-circulatin g drug carriers for sparingly soluble or amphiphilic drugs or diagnost ic agents is reviewed with the emphasis on the use of phosphatidyletha nolamine-polyethyleneoxide (PE-PEO) conjugates as structural amphiphil ic polymers for formulation of polymeric micelles. PE-PEO conjugates s pontaneously form particles with average diameter 10-30 nm depending o n the molecular weight of PEO block and which are stable upon dilution at ambient temperature. Topoisomerase II inhibitor ellipticine was sh own to be successfully incorporated into PE-PEO (5 kDa) conjugate mice lles in vitro. Percutaneous lymphatic delivery of amphiphilic diagnost ic agents incorporated into PE-PEO micelles was demonstrated using mag netic 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.