Research Of Deliverling Hydrophobic Drug Via Amphiphilic Thermosensitive Copolymer Carrier

Thermo-sensitive polymers can present sharp changes in physical structures or chemical properties in response to temperature. In recent years, those micelles self-assembled by amphiphilic thermo-sensitive copolymers have attracted much attention in the field of drug delivery system due to their controlled drug release and site-specific drug delivery.A series of poly(?-caprolactone)-poly(ethylene glycol)-poly(?-caprolactone) (PCL-PEG6000-PCL) copolymer has been successfully synthesized and their thermosensitive property has been investigated by test tube-inverting method. The prepared copolymers self-assembled in water to form micelles, and underwent temperature-dependent gel-sol transition, which was a flowing injectable solution at certain temperature and turned into a non-flowing gel at around physiological body temperature so as to be applied as drug depot. Furthermore, a hydrophobic small-molecule drug indomethacin (IND) was successfully encapsulated into PCL-PEG6000-PCL by dialysis method and reached high EE and LC with the solubility of IND improved more than 3000 folds. Pharmacodynamic study in vivo based on complete Freund's adjuvant-induced adjuvant arthritis model indicated that sustained therapeutic efficacy could be achieved through subcutaneous injection of IND-DS. Additionally, a novel injectable in situ gel-forming controlled drug delivery system based on coupling thermosensitive PCL-PEG6000-PCL and ?-cyclodextrin (PCEC-?-CD) was studied in this work. The drug encapsulating capacity has been improved by introducing ?-CD armed with PCEC copolymer. The IND-loaded PCEC-?-CD copolymer system (IND-PCD-DS) exhibited controlled release behavior in vitro. And the improvement of IND anti-inflammation effect on rats was significant by encapsulating in IND-PCD-DS on both carrageenan-induced acute and complete Freund's adjuvant-induced adjuvant arthritis model.