Intra-articular Administration of Chitosan Thermosensitive In Situ Hydrogels Combined With Diclofenac Sodium-Loaded Alginate Microspheres
Intra-articular Administration of Chitosan Thermosensitive In Situ Hydrogels Combined With Diclofenac Sodium-Loaded Alginate Microspheres
复制标题
壳聚糖热敏原位水凝胶联合双氯芬酸钠海藻酸钠微球的关节内给药
DOI：
10.1016/j.xphs.2015.11.019
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发表时间：
2016-01-01
影响因子：
3.8
通讯作者：
Song, Li
中科院分区：
文献类型：
--
作者：
Qi, Xiaole;Qin, Xiaoxue;Song, Li
本研究的目的是将海藻酸盐微球与壳聚糖温敏凝胶复合，制备出良好的关节内壳聚糖温敏水凝胶，并探讨其作为药物缓释系统促进抗炎作用的可能性。采用改进的乳化和/或凝胶法制备了双氯芬酸钠海藻酸微球，并将其分散到由壳聚糖和β-甘油磷酸组成的可注射温敏性水凝胶中。对最终的复合水凝胶的形态、流变性、体外释药、体内生物相容性和药效学行为进行了评价。优化处方在31.72℃+/-0.42℃下发生溶胶凝胶转变，5min内迅速转变为凝胶，缓释特性符合Ritger-Peppas方程，体外释药时间可延长至5d。此外，该复合水凝胶对实验性类风湿关节炎兔的抗炎效果优于药物溶液和纯壳聚糖水凝胶。这些结果表明，这些复合水凝胶有可能成为提高双氯芬酸钠疗效的潜在药物释放系统，为关节腔内给药提供了一个重要的技术平台。(C)2016年美国药剂师协会(R)。爱思唯尔公司出版，版权所有。
The aims of this study were to prepare fine intra-articular-administrated chitosan thermosensitive hydrogels combined with alginate microspheres and to investigate the possibility of those hydrogels as a drug delivery system for promoting the anti-inflammation effect. Diclofenac sodium containing alginate microspheres was prepared by a modified emulsification and/or gelation method and then dispersed into injectable thermosensitive hydrogels, consisting of chitosan and beta-glycerophosphate. The final combined hydrogels were evaluated in terms of their morphology properties, rheological properties, in vitro drug release, and in vivo biocompatibility and pharmacodynamics behaviors. The optimized formulation exhibited sol-gel transition at 31.72 +/- 0.42 degrees C and quickly turned into gel within 5 min, with sustained drug release characteristics followed Ritger-Peppas equation, which could prolong the in vitro drug release to 5 days. In addition, the anti-inflammation efficacy of the combined hydrogels in rabbits with experimental rheumatoid arthritis was higher than that of drug solution and pure chitosan hydrogels. Those results demonstrated that these combined hydrogels could become a potential drug delivery system for improving the therapeutic effect of diclofenac sodium and suggested an important technology platform for intra-articular administration. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.