Abstract:
OBJECTIVE To investigate temperature sensitivity of chitosan(CS)/carboxymethylchitosan(CMCS)/ glycerphosphate(GPS) hydrogel and study drug release profile of CS/CMCS/GPS hydrogel loading indomethacin and indomethacin/β-cyclodextrin inclusion complex. METHODS Using the method of inversion of test tube, temperature sensitivity of CS/CMCS/GPS hydrogel was studied under different ratio of CS and CMCS and GPS at various pH of the mixture solutions. β-cyclodextrin inclusion complex of indomethacin was prepared and characterized by IR. Drug loading and cumulative release of drug was detected by ultraviolet spectrophotometry. RESULTS The gelation time (GT) of CS/CMCS/GPS hydrogel was first increased from 370 s to 490 s and then decreased to 90 s at the considition of 37 ℃and pH 6.8 when the ratio in volume of 2%CS-2%CMCS-56% GPS from 10∶1∶2 to 10∶10∶2. The GT was within 66-407 s when the volume ratio of CS-CMCS-GPS was from 10∶3∶1 to 10∶3∶6. The suitable pH to gelate for CS/CMCS/GPS system was at 6.8-7.2. This system could rapidly be gelated at 37 ℃ under the appropriate volume ratio of CS/CMCS/GPS and pH. The in vitro dissolution showed that the cumulative release at 12 h of thermosensitive CS/CMCS/GPS gel loading indomethacin or indomethacin/ β-cyclodextrin inclusion complexes was 65.2% and 52.8%, respectively, which was significantly lower than that of raw indomethacin for 87.6% and inclusion compound of indomethacin for 82.1%. CONCLUSION CS/CMCS/GPS system with appropriate the volume ratio and pH can be gelable fastly at 37 ℃. Thermosensitive gel incorporating β-CD inclusion compound of drug showed more significant sustained release, and can be a good potential drug carrier for temperature sensitive and sustained drug delivery system.