Akbari Vajihe, Rezazadeh Mahboubeh, Ebrahimi Zahra
Department of Pharmaceutical Biothenology, Isfahan Pharmaceutical Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I. R. Iran.
Department of Pharmaceutics and Novel Drug Delivery System Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2020 Feb 20;15(1):97-106. doi: 10.4103/1735-5362.278719. eCollection 2020 Feb.
Bone regeneration can be accelerated by localized delivery of statins. Here, we aimed to evaluate the effect of two thermosensitive hydrogels containing rosuvastatin (RSV) on proliferation and differentiation of human osteoblast-like MG-63 cells.
Firstly, chitosan (CTS)/glycerophosphate (GP)/gelatin (G) thermosensitive hydrogel was prepared and characterized based on rheological properties, erosion, and release pattern of RSV and then the optimized mixture was loaded with nanoparticles containing RSV(NRSV). Secondly, the effect of NRSV-embedded in CTS/GP/G on cell viability, alkaline phosphate activity, and cell calcification was evaluated using MG-63 cells and compared with RSV-embedded into hyaluronic acid (HA)/Pluronic F127 (PF127) hydrogel.
FINDINGS / RESULTS: CTS/GP mixtures with 1 and 1.5 % gelatin existing in solution with low viscosity at 4 °C were solidified at 32-34 °C while the mixture containing 2% gelatin was jellified at room temperature. The gelation times of CTS/GP/G with 1 and 1.5% gelatin were 72 and 44 s, respectively. The hydrogel containing 3% w/v NRSV was also converted to a semisolid upon increasing the temperature to 33-36 °C. Due to the higher gel strength of CTS/GP/G compared to HA/PF127 hydrogel, the release rate of RSV from the NRSV-embedded CTS/GP/G hydrogel was significantly slower than that of HA/PF127 system. As revealed by alkaline phosphatase and mineralization assays, NRSV-embedded in CTS/GP/G hydrogel had the most promotive effect on differentiation of osteoblasts among other mixtures.
NRSV-embedded in CTS/GP/G hydrogel could be efficiently used in the future for bone defects such as osteoporosis and bone fractures.
他汀类药物的局部递送可加速骨再生。在此,我们旨在评估两种含瑞舒伐他汀(RSV)的热敏水凝胶对人成骨样MG-63细胞增殖和分化的影响。
首先,制备壳聚糖(CTS)/甘油磷酸酯(GP)/明胶(G)热敏水凝胶,并根据其流变学性质、侵蚀情况以及RSV的释放模式进行表征,然后将优化后的混合物负载含RSV的纳米颗粒(NRSV)。其次,使用MG-63细胞评估包埋于CTS/GP/G中的NRSV对细胞活力、碱性磷酸酶活性和细胞钙化的影响,并与包埋于透明质酸(HA)/泊洛沙姆F127(PF127)水凝胶中的RSV进行比较。
在4℃时,溶液中含有1%和1.5%明胶的CTS/GP混合物具有低粘度,在32 - 34℃时固化,而含有2%明胶的混合物在室温下凝胶化。含1%和1.5%明胶的CTS/GP/G的凝胶化时间分别为72秒和44秒。含3% w/v NRSV的水凝胶在温度升至33 - 36℃时也转变为半固体。由于CTS/GP/G水凝胶的凝胶强度高于HA/PF127水凝胶,包埋于CTS/GP/G水凝胶中的RSV的释放速率明显慢于HA/PF127体系。碱性磷酸酶和矿化分析表明,在其他混合物中,包埋于CTS/GP/G水凝胶中的NRSV对成骨细胞分化的促进作用最大。
包埋于CTS/GP/G水凝胶中的NRSV未来可有效地用于治疗骨质疏松症和骨折等骨缺损。