School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China; School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Int J Biol Macromol. 2018 Jul 15;114:462-469. doi: 10.1016/j.ijbiomac.2018.03.117. Epub 2018 Mar 22.
The aim of this study was to develop a novel nanostructured lipid carrier (NLC) based dual-responsive hydrogel for ocular drug delivery of quercetin (QN). NLC loaded with quercetin (QN-NLC) was prepared using melt-emulsification combined with ultra-sonication technique. A three-factor five-level central composite design (CCD) was employed to optimize the formulation of QN-NLC. The optimized QN-NLC presented a particle size of 75.54nm with narrow size distribution and high encapsulation efficiency (97.14%).QN-NLC was characterized by TEM and DSC. In addition, a pH and temperature dual-responsive hydrogel composed of carboxymethyl chitosan (CMCS) and poloxamer 407(F127) was constructed by a cross-linking reaction with a naturally occurring nontoxic crosslinking agent genipin (GP). FT-IR was employed to demonstrate that F127/CMCS hydrogel was successfully synthesized. The results of SEM analysis and swelling experiments indicated that F127/CMCS hydrogel was both temperature-responsive and pH-responsive. From the results of In vitro release studies, dual temperature and pH responsiveness of the hydrogel was demonstrated, and 80.52% of total quercetin was released from the QN-NLC based hydrogel (QN-NLC-Gel) within 3days, revealing QN-NLC-Gel released drug sustainably. Taken together, the developed NLC-based hydrogel is a promising drug delivery system for the ophthalmic application.
本研究旨在开发一种基于新型纳米结构化脂质载体（NLC）的双响应水凝胶，用于眼部递Quercetin（QN）。使用熔融乳化结合超声技术制备负载 Quercetin（QN-NLC）的 NLC。采用三因素五水平中心组合设计（CCD）优化 QN-NLC 的配方。优化后的 QN-NLC 粒径为 75.54nm，具有较窄的粒径分布和较高的包封效率（97.14%）。TEM 和 DSC 对 QN-NLC 进行了表征。此外，通过交联反应构建了由羧甲基壳聚糖（CMCS）和泊洛沙姆 407（F127）组成的 pH 和温度双响应水凝胶，交联剂为天然无毒交联剂京尼平（GP）。FT-IR 用于证明 F127/CMCS 水凝胶已成功合成。SEM 分析和溶胀实验结果表明，F127/CMCS 水凝胶具有温度和 pH 双重响应性。从体外释放研究结果来看，水凝胶具有双重温度和 pH 响应性，在 3 天内，基于 QN-NLC 的水凝胶（QN-NLC-Gel）中释放了 80.52%的总 Quercetin，表明 QN-NLC-Gel 可持续释放药物。综上所述，开发的基于 NLC 的水凝胶是一种有前途的眼部应用药物传递系统。
