期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 288, 期 2, 页码 207-218出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2004.09.026
关键词
controlled release; protein; thermosensitive; biodegradable polymer; lysozyme; biological activity
资金
- NICHD NIH HHS [HD 4137] Funding Source: Medline
The purpose of this study was to synthesize and characterize biodegradable and thermosensitive triblock copolymers for delivering protein at controlled rate in biologically active form for longer duration of time. A series of thermosensitive triblock copolymers with different block lengths (PLGA-PEG-PLGA) were synthesized by ring-opening polymerization of D,L-lactide and glycolide with polyethylene glycol (PEG) in the presence of stannous octoate. Compositions and molecular weight of triblock copolymers were characterized by H-1 NMR spectrometry and gel permeation chromatography, respectively. A single test-tube inverting method was employed to determine the sol-gel transition temperature. Lysozyme was used as a model protein. Lysozyme solution formulation was prepared with different triblock copolymers for in vitro release. Lysozyme concentration and its biological activity in the released sample were determined using a standard MicroBCA method and bacterial cell lysis method, respectively. The effects of varying block lengths and concentrations of copolymers on the in vitro release of lysozyme were evaluated. The release profiles from formulations showed a higher initial release followed by slower release up to 4 weeks. Increasing the block lengths of copolymers decreased burst release of lysozyme from 41.2 +/- 5.4% to 16.1 +/- 3.9%. Increasing copolymer concentrations decreased the drug release. Lysozyme in the 4 weeks released samples retained most of its biological activity (>80%). It is feasible to deliver protein in biologically active form for longer duration by varying block lengths and concentrations of triblock copolymers. (C) 2004 Elsevier B.V. All rights reserved.
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