Department of Pharmaceutics and Quality assurance, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425405, India.
Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425405, India.
Molecules. 2021 Mar 9;26(5):1485. doi: 10.3390/molecules26051485.
Ezetimibe (EZE) possesses low aqueous solubility and poor bioavailability and in addition, its extensive hepatic metabolism supports the notion of developing a novel carrier system for EZE. Ezetimibe was encapsulated into nanostructured lipid carriers (EZE-NLCs) via a high pressure homogenization technique (HPH). A three factor, two level (2) full factorial design was employed to study the effect of amount of poloxamer 188 (X1), pressure of HPH (X2) and number of HPH cycle (X3) on dependent variables. Particle size, polydispersity index (PDI), % entrapment efficiency (%EE), zeta potential, drug content and in-vitro drug release were evaluated. The optimized formulation displays pragmatic inferences associated with particle size of 134.5 nm; polydispersity index (PDI) of 0.244 ± 0.03; zeta potential of -28.1 ± 0.3 mV; % EE of 91.32 ± 1.8% and % CDR at 24-h of 97.11%. No interaction was observed after X-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies. EZE-NLCs (6 mg/kg/day p.o.) were evaluated in the high fat diet fed rats induced hyperlipidemia in comparison with EZE (10 mg/kg/day p.o.). Triglyceride, HDL-c, LDL-c and cholesterol were significantly normalized and histopathological evaluation showed normal structure and architecture of the hepatocytes. The results demonstrated the superiority of EZE-NLCs in regard to bioavailability enhancement, dose reduction and dose-dependent side effects.
依泽替米贝（EZE）具有低水溶性和差的生物利用度，此外，其广泛的肝脏代谢支持开发新型 EZE 载体系统的观点。依泽替米贝通过高压均质技术（HPH）被包封到纳米结构脂质载体（EZE-NLCs）中。采用三因素两水平（2）完全析因设计研究了泊洛沙姆 188 用量（X1）、HPH 压力（X2）和 HPH 循环数（X3）对因变量的影响。评价了粒径、多分散指数（PDI）、包封效率（% EE）、Zeta 电位、药物含量和体外药物释放。优化的配方显示出与粒径为 134.5nm、多分散指数（PDI）为 0.244±0.03、Zeta 电位为-28.1±0.3mV、包封效率（% EE）为 91.32±1.8%和 24 小时的累积药物释放（% CDR）为 97.11%相关的实用推断。X 射线衍射（XRD）和差示扫描量热法（DSC）研究后未观察到相互作用。与 EZE（10mg/kg/天 po）相比，在高脂肪饮食喂养的大鼠中评估了 EZE-NLCs（6mg/kg/天 po）在诱导高血脂症中的作用。甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和胆固醇显著正常化，组织病理学评估显示肝细胞结构和形态正常。结果表明，EZE-NLCs 在提高生物利用度、减少剂量和剂量依赖性副作用方面具有优越性。
