Synthesis and characterization of biodegradable polyrotaxane as a novel supramolecular-structured drug carrier

Abstract

Polyrotaxanes were synthesized as novel biodegradable polymers with supramolecular assembly and their properties evaluated in vitro. The synthesis of biodegradable polyrotaxanes consists of three steps: preparation of an inclusion complex consisting of α-cyclodextrins (α-CDs) and amino-terminated poly(ethylene glycol) (PEG); introduction of L-phenylalanine (L-Phe) at each complex terminal via peptide linkages; and hydroxypropylation of α-CDs in the polyrotaxanes. Succinimide ester of benzyloxycarbonyl-L-Phe was condensed with the terminal amino groups of the inclusion complex. ¹ H-NMR and GPC results showed that α-CDs were threaded onto a PEG chain and L-Phe moieties were introduced at each terminal of the PEG chain. Further, the amount of threaded α-CDs was found to be governed by the molecular weight of PEG. The hydroxypropylation of α-CDs improved the solubility of the polyrotaxanes in PBS (pH 7.4). The hydroxypropylated (HP-) polyrotaxanes were characterized by terminal peptide cleavage using papain. In vitro degradation of HP-polyrotaxanes revealed that HP-α-CDs threaded onto a PEG chain were released only when terminal peptide linkages were cleaved. Moreover, threaded HP-α-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 values were found to be independent of the molecular weight of HP-polyrotaxanes but to be affected by terminal hydrophobic moieties. It is proposed that our designed polyrotaxanes are feasible as novel drug carriers.

Keywords:

• Biodegradable polymer
• supramolecular assembly
• polyrotaxane
• drug delivery
• enzymatic degradation
• α-cyclodextrin
• poly(ethylene glycol)