Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr el Aini Street, Cairo, Egypt.
Department of Oral Medicine and Periodontology, Faculty of Dentistry, Cairo University, Kasr Al Aini Street, Cairo, Egypt.
Int J Pharm. 2020 Mar 15;577:119038. doi: 10.1016/j.ijpharm.2020.119038. Epub 2020 Jan 15.
This study aims to formulate and optimize simvastatin loaded chitosan-tripolyphosphate nanoparticles (SIM CS-TPP NPs) using ionic gelation method to provide a local delivery system that controls and sustains the release of simvastatin in the desired dose to promote bone regeneration. Box-Behnken design was adopted for optimization of the formulation variables of the prepared nanoparticles namely, CS percentage, TPP percentage and homogenization time. The optimized formula was selected and characterized by transmission electronic microscopy, in-vitro release, swelling index and storage stability. The ability of the optimum formula to stimulate bone regeneration upon implantation in bone defect generated in rabbits was also evaluated. The optimum SIM CS-TPP NPs had particle size of 106 nm, zeta potential of 43.3 mv, polydispersity index of 0.295 and entrapment efficiency of 98.78% and also showed good storage stability over the first month in addition to controlled and steady release over 2 weeks that effectively delivered simvastatin in a therapeutic dose needed for bone regeneration. Cone beam computed tomography 3D images, bone density measurements and histopathological analysis confirmed the high potential of SIM CS-TPP NPs in promoting bone regeneration in the generated defects compared to both the non-medicated formula and untreated groups after 6 weeks of implantation.
本研究旨在通过离子凝胶法制备和优化载辛伐他汀壳聚糖-三聚磷酸酯纳米粒（SIM CS-TPP NPs），提供一种局部递送系统，以控制和维持所需剂量的辛伐他汀释放，从而促进骨再生。采用 Box-Behnken 设计对所制备纳米粒的处方变量（CS 百分比、TPP 百分比和均质时间）进行优化。选择并通过透射电子显微镜、体外释放、溶胀指数和储存稳定性对优化配方进行表征。还评估了最优配方在兔骨缺损中植入后刺激骨再生的能力。最优的 SIM CS-TPP NPs 的粒径为 106nm，Zeta 电位为 43.3mV，多分散指数为 0.295，包封效率为 98.78%，并且在最初一个月内具有良好的储存稳定性，此外，还能在 2 周内实现持续、稳定的释放，有效递送到促进骨再生所需的治疗剂量的辛伐他汀。锥形束 CT 3D 图像、骨密度测量和组织病理学分析证实，与未载药配方和未处理组相比，SIM CS-TPP NPs 在植入 6 周后，在生成的缺陷中具有更高的促进骨再生潜力。
