He Miao, Wang Haiyan, Dou Wei, Chou Guixin, Wei Xiaohui, Wang Zhengtao
The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai R&D Center for Standardization of Chinese Medicines, Shanghai 201210, China.
The Third People's Hospital of Jinan, Jinan 250132, China.
Int J Biol Macromol. 2016 Oct;91:1101-9. doi: 10.1016/j.ijbiomac.2016.06.076. Epub 2016 Jun 23.
This study aimed to develop injectable norisoboldine (NOR) chitosan microspheres formulated through the emulsion cross-linking method. The formulation was optimized using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The morphology, size, physicochemical characterization and in vitro release behavior of the optimized formulation were evaluated. Scanning electron micrographs (SEM) indicated that the microspheres were spherical with a smooth surface. The encapsulation efficiency and drug loading content of the microspheres were 38.89%±1.72% and 4.25%±0.15%, respectively, with an average size of 105μm. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed the absence of a drug-polymer interaction and the amorphous nature of an entrapped drug. Analysis results of drug release in vitro show the burst release of the microsphere in 2h and a slow progression afterward. In vivo studies using Sprague-Dawley rats revealed that the NOR-loaded chitosan microspheres were biocompatible. This study suggests that the BBD with desired formulation could provide a suitable drug delivery system of chitosan microspheres.
本研究旨在通过乳化交联法制备可注射的去甲紫堇碱（NOR）壳聚糖微球。采用响应面法（RSM）和三水平、三因素的Box-Behnken设计（BBD）对制剂进行优化。对优化后的制剂的形态、尺寸、理化性质及体外释放行为进行了评价。扫描电子显微镜（SEM）照片显示微球呈球形，表面光滑。微球的包封率和载药量分别为38.89%±1.72%和4.25%±0.15%，平均粒径为105μm。傅里叶变换红外光谱（FT-IR）、差示扫描量热法（DSC）和X射线衍射（XRD）表明不存在药物-聚合物相互作用，且包封药物为无定形。体外药物释放分析结果显示微球在2小时内有突释，随后释放缓慢。使用Sprague-Dawley大鼠进行的体内研究表明，载NOR的壳聚糖微球具有生物相容性。本研究表明，具有理想制剂的BBD可为壳聚糖微球提供合适的药物递送系统。
