摘要
目的:采用安全性高、生物相容性好的常用凝胶材料制备白藜芦醇原位漂浮凝胶,并对处方进行优化,获得具有温敏性质的可漂浮于膀胱内并长时间持续释放药物的凝胶剂,用于膀胱癌的膀胱灌注化疗。方法:以泊洛沙姆407、泊洛沙姆188、海藻酸钠、碳酸钙、碳酸氢铵为辅料,冷溶法制备凝胶;以胶凝温度、胶凝时间为指标,采用星点设计-响应面法对泊洛沙姆407、泊洛沙姆188、碳酸氢铵的用量进行优化;对优化处方进行温敏性能、漂浮性能和释药性能评价。结果:最优处方为白藜芦醇30%,泊洛沙姆407 17.2%,泊洛沙姆188 5.5%,海藻酸钠0.15%,碳酸钙0.06%,碳酸氢铵0.15%。该处方的胶凝温度为28℃~29℃,胶凝时间为50 s,药物以扩散方式从漂浮凝胶中缓慢释放,持续释放时间超过48 d。结论:白藜芦醇原位漂浮凝胶具有膀胱内长时间持续释放药物的性质,可以作为膀胱癌治疗中膀胱灌注化疗的替代给药形式,具有提高患者依从性的优点。
Objective: To prepare and optimize the formulation of resveratrol in situ floating gel using common gel materials with high safety and good biocompatibility, in order to obtain a temperature-sensitive gel that can float and continuously release drug in bladder and can be used for bladder perfusion in chemotherapy of bladder cancer. Methods: The gel was prepared by cold dissolution method. Poloxam 407, Poloxam 188, sodium alginate, calcium carbonate and ammonium bicarbonate were used as main excipients. Gelling temperature and gelling time were selected as the indicators to optimize the quantity of poloxamer 407, poloxamer 188 and calcium carbonate in formulation by central combination-response surface method. Temperature sensitivity, floating performance and drug releasing performance of the optimized formulation were evaluated. Results: The optimal formulation was composed of resveratrol 30%, Poloxam 407 17.2%, Poloxam 188 5.5%, sodium alginate 0.15%, calcium carbonate 0.06%, ammonium bicarbonate 0.15%. The gelling temperature was 28~29 ℃ and the gelling time was 50 s. The drug were released from the gel in a way of diffusion for more than 48 days. Conclusion: The resveratrol in situ floating gel had the property of continuous drug release for a long time in bladder. It can be used as an alternative form of bladder perfusion chemotherapy in the treatment of bladder cancer to improve patient compliance.
作者
吴文丽
孙春艳
郑光艳
王立红
吕元菊
刘泽梅
车鑫
WU Wen-li;SUN Chun-yan;ZHENG Guang-yan;WANG Li-hong;LV Yuan-ju;LIU Ze-mei;CHE Xin(Traditional Chinese Medicine of Guizhou University,Guiyang 550000,China;Shandong Pharmaceutical and Food Vocational College,Zibo 255000,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2023年第3期294-300,共7页
Chinese Journal of New Drugs
基金
贵州省中管局项目(QZYY-2020-044)
贵州省科技厅项目(黔科合基础-ZK[2021]一般524)。
关键词
膀胱癌
膀胱灌注
白藜芦醇
原位凝胶
持续释放
bladder cancer
bladder perfusion
resveratrol
in situ gel
sustained-release
