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含姜黄素负载白蛋白纳米粒的热敏性眼用原位凝胶的优化与评价

Optimization and evaluation of a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles.

作者信息

Lou Jie, Hu Wenjing, Tian Rui, Zhang Hua, Jia Yuntao, Zhang Jingqing, Zhang Liangke

机构信息

Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China.

Chongqing Xijiao Hospital, Chongqing, People's Republic of China.

出版信息

Int J Nanomedicine. 2014 May 21;9:2517-25. doi: 10.2147/IJN.S60270. eCollection 2014.

Abstract

This study aimed to optimize and evaluate a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles (Cur-BSA-NPs-Gel). Albumin nanoparticles were prepared via a desolvation method, and the gels were prepared via a cold method. The central composite design and response surface method was used to evaluate the effects of varying Pluronic F127 and Pluronic F68 concentrations on the sol-gel transition temperature, which is an indicator of optimum formulations. The optimized formulation was a free-flowing liquid below 30.9°C that transformed into a semi-solid gel above 34.2°C after dilution with simulated tear fluid. Results of the in vitro release and erosion behavior study indicated that Cur-BSA-NPs-Gel achieved superior sustained-release effects and that incorporation of albumin nanoparticles exerted minimal effects on the gel structure. In addition, in vivo ophthalmic experiments employing Cur-BSA-NPs-Gel were subsequently performed in rabbits. In vivo eye irritation results showed that Cur-BSA-NPs-Gel might be considered safe for ophthalmic drug delivery. The in vivo study also revealed that the formulation could significantly increase curcumin bioavailability in the aqueous humor. In conclusion, the optimized in situ gel formulation developed in this work has significant potential for ocular application.

摘要

本研究旨在优化和评估一种含载姜黄素白蛋白纳米粒(Cur-BSA-NPs-Gel)的热敏性眼用原位凝胶。通过去溶剂法制备白蛋白纳米粒,采用冷法制备凝胶。运用中心复合设计和响应面法评估不同浓度的泊洛沙姆F127和泊洛沙姆F68对溶胶-凝胶转变温度的影响,溶胶-凝胶转变温度是最佳配方的一个指标。优化后的配方在30.9°C以下为自由流动液体,用模拟泪液稀释后在34.2°C以上转变为半固体凝胶。体外释放和侵蚀行为研究结果表明,Cur-BSA-NPs-Gel具有优异的缓释效果,并且白蛋白纳米粒的加入对凝胶结构影响极小。此外,随后在兔子身上进行了使用Cur-BSA-NPs-Gel的体内眼部实验。体内眼刺激结果表明,Cur-BSA-NPs-Gel可被认为用于眼部给药是安全的。体内研究还表明,该配方可显著提高姜黄素在房水中的生物利用度。总之,本研究开发的优化原位凝胶配方在眼部应用方面具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aed5/4039420/18b3759a4f98/ijn-9-2517Fig1.jpg

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