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Acta Biomater. 2013 Jun;9(6):6953-63. doi: 10.1016/j.actbio.2013.02.005. Epub 2013 Feb 13.

Thermosensitive β-cyclodextrin modified poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) micelles prolong the anti-inflammatory effect of indomethacin following local injection.

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College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.


A novel biodegradable and injectable in situ gel-forming controlled drug delivery system based on thermosensitive β-cyclodextrin-modified poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) co-polymer (PCEC-β-CD) was studied in this work. The drug encapsulating capacity has been improved by introducing β-CD bound to the PCEC co-polymer. The prepared PCEC-β-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-β-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-β-CD micelles.

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