期刊
ACTA BIOMATERIALIA
卷 9, 期 6, 页码 6953-6963出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2013.02.005
关键词
Thermosensitive micelle; beta-Cyclodextrin; Poly(epsilon-caprolactone); Indomethacin; Inflammation
资金
- National Natural Science Funds for Excellent Young Scholar [81222047]
- Major Scientific and Technological Special Project for New Drugs Creation [2011ZX 09501-001-04]
A novel biodegradable and injectable in situ gel-forming controlled drug delivery system based on thermosensitive beta-cyclodextrin-modified poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) co-polymer (PCEC-beta-CD) was studied in this work. The drug encapsulating capacity has been improved by introducing beta-CD bound to the PCEC co-polymer. The prepared PCEC-beta-CD co-polymers self-assembled in water to form micelles, and underwent a temperature-dependent gel-sol transition, which was in the form of a flowing injectable solution at low temperatures but became a non-flowing gel at around physiological body temperature. Furthermore, a small hydrophobic drug molecule indomethacin (IND) was successfully encapsulated in PCEC-beta-CD micelles by dialysis at a high encapsulation efficiency and drug loading capacity. The IND-loaded micelles (IND-M) exhibited controlled release in vitro. Additionally, a pharmacodynamic study in vivo based on both the carrageenan-induced acute and complete Freund's adjuvant-induced adjuvant arthritis models indicated that sustained therapeutic efficacy could be achieved through subcutaneous injection of IND-loaded micelles. A significant improvement in the anti-inflammatory effect of IND in rats occurred on encapsulation in PCEC-beta-CD micelles. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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