SYNTHESIS AND CHARACTERIZATION OF BIODEGRADABLE POLYROTAXANE AS A NOVEL SUPRAMOLECULAR-STRUCTURED DRUG CARRIER

Polyrotaxanes were synthesized as novel biodegradable polymers with su pramolecular assembly and their properties evaluated in vitro. The syn thesis of biodegradable polyrotaxanes consists of three steps: prepara tion of an inclusion complex consisting of alpha-cyclodextrins (alpha- CDs) and amino-terminated poly(ethylene glycol) (PEG); introduction of L-phenylalanine (L-Phe) at each complex terminal via peptide linkages ; and hydroxypropylation of alpha-CDs in the polyrotaxanes. Succinimid e ester of benzyloxycarbonyl-L-Phe was condensed with the terminal ami no groups of the inclusion complex. H-1-NMR and GPC results showed tha t alpha-CDs were threaded onto a PEG chain and L-Phe moieties were int roduced at each terminal of the PEG chain. Further, the amount of thre aded alpha-CDs was found to be governed by the molecular weight of PEG . The hydroxypropylation of alpha-CDs improved the solubility of the p olyrotaxanes in PBS (pH 7.4). The hydroxypropylated (HP-) polyrotaxane s were characterized by terminal peptide cleavage using papain. In vit ro degradation of HP-polyrotaxanes revealed that HP-alpha-CDs threaded onto a PEG chain were released only when terminal peptide linkages we re cleaved. Moreover, threaded HP-alpha-CDs onto a PEG chain was found to be completely released. Kinetics of terminal peptide cleavage were also evaluated by catalytic efficiency (k(cat)/K-m). The k(cat)/K-m v alues were found to be independent of the molecular weight of HP-polyr otaxanes but to be affected by terminal hydrophobic moieties. It is pr oposed that our designed polyrotaxanes are feasible as novel drug carr iers.