壳聚糖-羧甲基壳聚糖凝胶的温敏性及体外药物缓释试验

Temperature Sensitivity and Sustained in Vitro Drug Release of Chitosan-Carboxymethylchitosan Hydrogel

关键词:  壳聚糖  温敏性  吲哚美辛  β-环糊精  缓释

Key words:  chitosan  thermosensitive  indomethacin  β-cyclodextrin  sustained release

摘要:

目的 研究壳聚糖/羧甲基壳聚糖/甘油磷酸钠(CS/CMCS/GPS)体系水凝胶的温敏性，载药凝胶以及共混β-环糊精(β-CD)包合物对药物的缓释性能。方法 试管倒置法研究不同配比，不同pH值对CS/CMCS/GPS体系温敏凝胶化性能的影响；饱和水溶液法制备吲哚美辛/β-CD包合物，红外光谱表征包合物；紫外分光光度法测定包合物载药量和药物的累积释放度。结果 2%CS-2%CMCS-56%GPS体积比从10∶1∶2变为10∶10∶2（体系pH 6.8），37 ℃下凝胶化时间由370 s升至490 s，后又降至90 s；三者体积比从10∶3∶1变为10∶3∶6(体系pH 6.8)，37 ℃下凝胶化时间从407 s降至66 s。pH值在6.8~7.2范围适合于体系凝胶化。调节体积比及合适的pH值，在37 ℃下可实现CS/CMCS/GPS体系快速凝胶化。以吲哚美辛和吲哚美辛/β-CD包合物为模型药物，载有吲哚美辛温敏凝胶12 h的累积释放度为65.2%，载有吲哚美辛/β-CD包合物温敏凝胶累积释放度为52.8%，而吲哚美辛原药12 h的累积释放度为87.6%，吲哚美辛/β-CD包合物的累积释放度为82.1%。结论 一定体积配比CS/CMCS/GPS体系在37 ℃具有快速凝胶特性，β-CD包合物与温敏性凝胶共混，对药物具有更加明显的缓释作用。

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.