title: Thermosensitive β-cyclodextrin modified poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) micelles prolong the anti-inflammatory effect of indomethacin following local injection.
abstract: 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.
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.
authors: Xiawei
authors: X
authors: Wei
authors: Xinyi
authors: X
authors: Lv
authors: Qinghe
authors: Q
authors: Zhao
authors: Liyan
authors: L
authors: Qiu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D004357:Drug Synergism; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D015552:Injections, Intralesional; D008297:Male; D008422:Materials Testing; D008657:Metabolic Clearance Rate; D008823:Micelles; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D013696:Temperature; D016896:Treatment Outcome; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D008823:Micelles; D011091:Polyesters; D047392:beta-Cyclodextrins; C492324:poly(epsilon-caprolactone)-poly(oxyethylene)-poly(epsilon-caprolactone); D011092:Polyethylene Glycols; C031215:betadex; D007213:Indomethacin