INCORPORATION OF WATER-INSOLUBLE ANTICANCER DRUG INTO POLYMERIC MICELLES AND CONTROL OF THEIR PARTICLE-SIZE

A water-insoluble anticancer drug, KRN 5500 (KRN), was incorporated in to polymeric micelles forming from poly(ethylene glycol-poly(amino aci d) block copolymers by physical entrapment utilizing hydrophobic inter actions between this drug and the poly(amino acid) chain block of the block copolymers. Three block copolymers were examined for this incorp oration; poly(ethylene glycol)-poly(beta-benzyl L-aspartate) (PEG-PBLA ) and its two derivatives obtained by partial hydrolysis at the beta-b enzyl L-aspartate (BLA) units (PEG-P(Asp, BLA)) and by partial cetyl e ster substitution at the BLA units (PEG-P(C-16 BLA)), respectively. Am ong these block copolymers, considerable effects of the cetyl esterifi cation were seen on KRN yield and particle size. Considerable differen ces in the KRN incorporation yield and particle size were also observe d between DMF and DMS used as solvent to dissolve KRN and the block co polymers. Sonication was turned out to be an effective method to obtai n a polymer micelles fraction in high efficiency, and sonication was c onsidered to work for separating intermicellar associates into dispers ed micelles. A KRN incorporation procedure by dialysis using PEG-P(C-1 6, BLA) and DMSO las solvent) followed by sonication brought about pol ymeric micelles of 71 nm in weight-average diameter. This shows succes sful incorporation of a water-insoluble drug into polymeric micelles b y optimizing block copolymer structure and incorporation conditions. ( C) 1998 Elsevier Science B.V. All rights reserved.