A macromolecular prodrug-type injectable polymer composed of poly(depsipeptide-co-lactide)-g-PEG for sustained release of drugs

作者：Takahashi Akihiro; Umezaki Masaya; Yoshida Yasuyuki; Kuzuya Akinori; Ohya Yuichi^*

来源：Polymers for Advanced Technologies, 2014, 25(11): 1226-1233.

DOI：10.1002/pat.3265

• injectable polymers
• macromolecular prodrug
• temperature-responsive sol-to-gel transition
• controlled release
• graft copolymer

We propose a macromolecular prodrug strategy of an injectable polymer (IP) system for continuous and sustained release of water-soluble low-molecular-weight drugs. A biodegradable graft copolymer-type IP covalently immobilizing model drugs via hydrolyzable ester bonds was synthesized through the coupling reaction of poly(depsipeptide-co-dl-lactide), P(DG-dl-LA), having reactive carboxylic acid side-chain groups with the amino derivative of a model drug (levofloxacin [LEV]) and monomethoxy-poly(ethylene glycol) (PEG). The solution of the obtained graft copolymer-type IP/model drug conjugate exhibited a temperature-responsive sol-to-gel transition between room temperature and body temperature in phosphate buffer solution, similar to P(GD-dl-LA)-g-PEG without LEV. The immobilization of the LEV molecule onto P(DG-dl-LA)-g-PEG did not have a significant influence on the sol-to-gel transition behavior, physical properties, or in vitro degradation rates of the hydrogels. The in vitro release of LEV derivatives from the P(DG-dl-LA)-g-PEG/LEV hydrogel in phosphate buffer solution was continuous for 11weeks, which corresponded to the degradation period of the hydrogel, and slower than that from the control hydrogels prepared from P(DG-dl-LA)-g-PEG and PLGA-b-PEG-b-PLGA that physically entrapped LEV molecules. These results suggest that the covalent attachment strategy is effective in achieving sustained release of low-molecular-weight drugs in IP systems and can be applied to drug delivery devices for highly bioactive drugs.

• 出版日期2014-11