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

A polyrotaxane consisting of α-cyclodextrins (α-CDs) and α,ω-di(glycylglycyne) polyoxyethylene (α,ω-di(Gly-Gly)-PEG) capped with tyrosine was synthesized as a drug carrier and its in vitro degradation by aminopeptidase M was demonstrated. α,ω-Di(Gly-Gly)-PEG was prepared by condensation reaction between terminal amino-groups in α-(3-aminopropyl)-ω-(3-aminopropyl) polyoxyethylene and succinimide ester of N-tert-butyloxycarbonyl (Boc)-Gly-Gly, followed by the deprotection of Boc group via acidic hydrolysis. A polypseudorotaxane consisting of α-CDs and α,ω-di(Gly-Gly)-PEG was prepared in the mixture of water and dimethylsulfoxide. The polyrotaxane was successfully synthesized by condensation reaction between the amino-groups in the pseudopolyrotaxane and p-nitrophenyl ester of carbobenzoxy L-tyrosine. The addition of 1-hydroxy-1H-benzotriazole on the reaction was found to increase the yield and the number of α-CDs in the polyrotaxane. Hydroxypropylation of the polyrotaxane improved the solubility in aqueous solutions and many kinds of organic solvents. In vitro degradation of the hydroxypropylated (HP-)polyrotaxane revealed that HP-α-CDs in the HP-polyrotaxane were released in the presence of aminopeptidase M. These results suggest that the supramolecular dissociation will be triggered by the action of extracellular enzymes and lead to a new mechanism of drug release from polymeric drug carriers.