Chitkara College of Pharmacy, Chitkara University, Punjab, India.
Curr Drug Targets. 2023;24(13):1066-1078. doi: 10.2174/1389450124666230915092910.
Statins, especially simvastatin promote bone formation by stimulating the activity of osteoblasts and suppressing osteoclast activity the BMP-Smad signaling pathway. Statins present the liver first-pass metabolism. This study attempts to fabricate and evaluate simvastatin functionalized hydroxyapatite encapsulated in poly(lactic-co-glycolic) acid (PLGA) nanoparticles (HSIM-PLGA NPs) administered subcutaneously with sustained release properties for effective management of osteoporosis.
Simvastatin functionalized hydroxyapatite (HSIM) was prepared by stirring and validated by docking studies, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Further, HSIM-loaded PLGA nanoparticles (HSIM-PLGA NPs) were developed the solvent emulsification method. The nanoparticles were evaluated for zeta potential, particle size, entrapment efficiency, stability studies, and drug release studies. binding affinity of nanoparticles for hydroxyapatite was also measured. Bone morphology and its effect on bone mineral density were examined by using a glucocorticoid-induced osteoporosis rat model.
The optimized nanoparticles were found to be amorphous and showed no drug-polymer interaction. The particle size of formulated nanoparticles varied from 196.8 ± 2.27nm to 524.8 ± 5.49 nm and the entrapment efficiency of nanoparticles varied from 41.9 ± 3.44% to 70.8 ± 4.46%, respectively. The nanoparticles showed sustained release behaviour (75% in 24 hr) of the drug followed by non-fickian drug release. The nanoparticles exhibited high binding affinity to bone cell receptors, increasing bone mineral density. A significant difference in calcium and phosphorous levels was observed in disease and treatment rats. Porous bone and significant improvement in porosity were observed in osteoporotic rats and treated rats, respectively ( < 0.05).
Bone-targeting nanoparticles incorporating functionalized simvastatin can target bone. Thus, in order to distribute simvastatin subcutaneously for the treatment of osteoporosis, the developed nanoparticles may act as a promising approach.
他汀类药物，特别是辛伐他汀，通过刺激成骨细胞活性和抑制破骨细胞活性来促进骨形成——BMP-Smad 信号通路。他汀类药物具有肝脏首过代谢效应。本研究尝试制备并评估辛伐他汀功能化羟基磷灰石包封于聚（乳酸-共-乙醇酸）（PLGA）纳米粒子（HSIM-PLGA NPs）中，通过皮下给予具有持续释放特性的纳米粒子来有效治疗骨质疏松症。
通过搅拌制备辛伐他汀功能化羟基磷灰石（HSIM），并通过对接研究、傅里叶变换红外光谱（FTIR）、扫描电子显微镜（SEM）和 X 射线衍射（XRD）进行验证。进一步，通过溶剂乳化法制备 HSIM 负载的 PLGA 纳米粒子（HSIM-PLGA NPs）。对纳米粒子进行zeta 电位、粒径、包封效率、稳定性研究和药物释放研究。还测量了纳米粒子与羟基磷灰石的结合亲和力。通过糖皮质激素诱导的骨质疏松大鼠模型，观察骨形态及其对骨密度的影响。
优化后的纳米粒子呈无定形态，且无药物-聚合物相互作用。所制备的纳米粒子的粒径为 196.8±2.27nm 至 524.8±5.49nm，纳米粒子的包封效率为 41.9±3.44%至 70.8±4.46%。纳米粒子表现出药物的持续释放行为（24 小时内 75%释放），随后是非菲克扩散药物释放。纳米粒子表现出对骨细胞受体的高结合亲和力，增加了骨密度。在疾病和治疗大鼠中观察到钙和磷水平的显著差异。骨质疏松症大鼠和治疗大鼠分别观察到多孔骨和骨孔隙度的显著改善（<0.05）。
将辛伐他汀功能化的骨靶向纳米粒子可以靶向骨骼。因此，为了将辛伐他汀经皮给药用于治疗骨质疏松症，所开发的纳米粒子可能是一种很有前途的方法。
