Synthesis and characterization of an oligopeptide-terminated polyrotaxane as a drug carrier

A polyrotaxane consisting of alpha -cyclodextrins (alpha -CDs) and alpha,om ega -di(glycylglycyne) polyoxyethylene (alpha,omega -di(Gly-Gly)-PEG) cappe d with tyrosine was synthesized as a drug carrier and its in vitro degradat ion by aminopeptidase M was demonstrated alpha,omega -Di(Gly-Gly)-PEG was p repared by condensation reaction between terminal amino-groups in alpha-(3- aminopropyl)-omega-(3-aminopropyl) polyoxyethylene and succinimide ester of N-tert-butyloxycarbonyl (Boc)-Gly-Gly,followed by the deprotect ion of Boc group via acidic hydrolysis. A polypseudorotaxane consisting of alpha -CDs and alpha,omega -di(Gly-Gly)-PEG was prepared in the mixture of water and dimethylsulfoxide, The polyrotaxane was successfully synthesized by condens ation reaction between the amino-groups in the pseudopolyrotaxane and p-nit rophenyl ester of carbobenzoxy L-tyrosine. The addition of 1-hydroxy-1H-ben zotriazole on the reaction was found to Increase the yield and the number o f alpha -CDs in the polyrotaxane. Hydroxypropylation of the polyrotaxane im proved the solubility in aqueous solutions and many kinds of organic solven ts. In vitro degradation of the hydroxypropylated (HP-)polyrotaxane reveale d that HP-alpha -CDs in the HP-polyrotaxane were released in the presence o f aminopeptidase M. These results suggest that the supramolecular dissociat ion will be triggered by the action of extracellular enzymes and lead to a new mechanism of drug release from polymeric drug carriers. Copyright (C) 2 000 John Wiley & Sons, Ltd.