Delan Wisam Khalaf, Ali Isra H, Zakaria Mai, Elsaadany Basma, Fares Ahmed R, ElMeshad Aliaa N, Mamdouh Wael
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr el Aini Street, Cairo 11562, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, University of Sadat City, P.O. Box 32897, Sadat City, Egypt; Department of Chemistry, School of Sciences and Engineering, The American University in Cairo (AUC), AUC Avenue, P.O. Box 74, New Cairo 11835, Egypt.
Int J Biol Macromol. 2022 Dec 1;222(Pt B):2399-2413. doi: 10.1016/j.ijbiomac.2022.10.026. Epub 2022 Oct 8.
This study aims at preparing electrospun PVA NFs incorporating simvastatin/chitosan nanoparticles (SIM CS NPs) as a controlled drug eluting scaffold for bone regeneration. Optimization was performed by Design Expert® software through establishing two factor, three level factorial design, where the independent variables were the applied voltage, flow rate and PVA solution/SIM CS NPs ratio. Formulation variables values for the optimized formula were 18KV, 0.5 mL/h, and 3:1 respectively. NFs diameter and mesh pore size were chosen as the dependent variables. The optimized NFs were evaluated morphologically, chemically, and physically. Additionally, in-vitro SIM release from the scaffolds was investigated along 24 days. Optimum NFs possessed 136 nm diameter size and 6.5 nm porosity. Also, they showed sustained SIM release for 24 days to achieve the desired goal in bone regeneration. The optimized NFs were implanted within induced bone defects in rabbits. In-vivo assessments were performed through cone beam computed tomography 3D images, bone density measurements, histological analysis and bone morphogenetic protein 2 (BMP 2) level. The obtained results proved the high potential of the optimized NFs in promoting bone regeneration compared to untreated group, non-medicated NFs group, free SIM group and NFs loaded with SIM group after 6 weeks of implantation.
本研究旨在制备含有辛伐他汀/壳聚糖纳米颗粒（SIM CS NPs）的电纺聚乙烯醇纳米纤维（PVA NFs），作为用于骨再生的控释药物支架。通过Design Expert®软件进行优化，建立了二因素三水平析因设计，其中自变量为施加电压、流速和PVA溶液/SIM CS NPs比例。优化配方的配方变量值分别为18KV、0.5 mL/h和3:1。选择纳米纤维直径和网孔尺寸作为因变量。对优化后的纳米纤维进行了形态学、化学和物理评估。此外，还研究了支架在24天内的体外辛伐他汀释放情况。最佳纳米纤维的直径尺寸为136 nm，孔隙率为6.5 nm。此外，它们显示出辛伐他汀持续释放24天，以实现骨再生的预期目标。将优化后的纳米纤维植入兔诱导性骨缺损处。通过锥形束计算机断层扫描3D图像、骨密度测量、组织学分析和骨形态发生蛋白2（BMP 2）水平进行体内评估。所得结果证明，与植入6周后的未治疗组、未载药纳米纤维组、游离辛伐他汀组和载有辛伐他汀的纳米纤维组相比，优化后的纳米纤维在促进骨再生方面具有很高的潜力。
