Synthesis and characterization of biodegradable polyrotaxane as a novel supramolecular-structured drug carrier.
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 alpha-cyclodextrins (alpha-CDs) and amino-terminated poly(ethylene glycol) (PEG); introduction of L-phenylalanine (L-Phc) at each complex terminal via peptide linkages: and hydroxypropylation of alpha-CDs in the polyrotaxanes. Succinimide ester of benzyloxycarbonyl-L-Phe was condensed with the terminal amino groups of the inclusion complex. 1H-NMR and GPC results showed that alpha-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 alpha-CDs was found to be governed by the molecular weight of PEG. The hydroxypropylation of alpha-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-alpha-CDs threaded onto a PEG chain were released only when terminal peptide linkages were 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 (kcat/K(m)). The kcat/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.
Ooya
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T
School of Materials Science, Japan Advanced Institute of Science and Technology, Ishikawa, Japan.
Yui
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N
D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001673:Biodegradation, Environmental; D003505:Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007700:Kinetics; D008422:Materials Testing; D015394:Molecular Structure; D010206:Papain; D010649:Phenylalanine / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D047391:alpha-Cyclodextrins
D001672:Biocompatible Materials; D003505:Cyclodextrins; D004337:Drug Carriers; D011108:Polymers; D047391:alpha-Cyclodextrins; D011092:Polyethylene Glycols; D010649:Phenylalanine; D010206:Papain; C032613:alpha-cyclodextrin