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

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.