Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Drug Deliv. 2021 Dec;28(1):642-654. doi: 10.1080/10717544.2021.1902023.
Eplerenone (EPL) is a selective mineralocorticoid receptor antagonist used for treatment of chronic central serous chorioretinopathy which characterized by accumulation of subretinal fluid causing a localized area of retinal detachment. unfortunately, EPL suffers from poor oral bioavailability due to poor aqueous solubility in addition to high hepatic first pass metabolism.
Aiming to improve its oral bioavailability, EPL-loaded nanostructured lipid carriers (NLCs) were prepared by the emulsification solvent evaporation method and evaluated for particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). A D-optimal design was used for study the effect of liquid lipid to solid lipid ratio, surfactant type and percentage on PS, PDI, EE%, and for data optimization. The optimized EPL-loaded NLCs system was further evaluated using drug release and permeation studies through rabbit intestine in comparison to EPL aqueous suspension. The physicochemical properties of the drug in the optimized system were further examined using FT-IR and X-ray diffraction studies.
The resultant NLCs showed small PS (100.85-346.60 nm), homogenous distribution (0.173-0.624), negatively charged particles (ZP -20.20 to -36.75 mV), in addition to EE% (34.31-70.64%). The optimized EPL-loaded NLCs system with a desirability value of 0.905 was suggested through the Design expert software, containing liquid to solid lipid ratio (2:1) in presence of 0.43%w/v Pluronic F127 as a surfactant. The optimized EPL-loaded NLCs system showed a PS of 134 nm and PDI of 0.31, in addition to high EE% (76 ± 6.56%w/w), and ZP (-32.37 mV). The permeation study showed two-fold higher drug permeation through rabbit intestine compared to that from the aqueous drug suspension after 24 h, confirming the ability of optimized EPL-loaded NLCs system as successful oral targeting delivery carrier.
Our results pave the way for a new oral nanotherapeutic approach toward CSCR treatment. study is currently under investigation.
依普利酮（EPL）是一种选择性的盐皮质激素受体拮抗剂，用于治疗慢性中心性浆液性脉络膜视网膜病变，其特征是眼内液体积聚导致局部视网膜脱离。不幸的是，EPL 由于水溶性差和肝脏首过代谢高，口服生物利用度较差。
为了提高其口服生物利用度，采用乳化溶剂蒸发法制备了载依普利酮的纳米结构脂质载体（NLCs），并对其粒径（PS）、多分散指数（PDI）、Zeta 电位（ZP）和包封效率（EE%）进行了评价。采用 D-最优设计研究了液/固脂质比、表面活性剂类型和百分比对 PS、PDI、EE%的影响，并对数据进行了优化。将优化后的 EPL 载 NLCs 系统与 EPL 水混悬液进行比较，进一步通过兔肠的药物释放和渗透研究进行评价。采用傅里叶变换红外光谱（FT-IR）和 X 射线衍射研究进一步考察了优化系统中药物的物理化学性质。
所得 NLCs 的 PS（100.85-346.60nm）较小、分布均匀（0.173-0.624）、带负电荷的粒子（ZP-20.20 至-36.75mV），EE%（34.31-70.64%）高。通过 Design expert 软件建议采用含有 0.43%w/v 泊洛沙姆 F127 的液/固脂质比（2:1）的具有 0.905 理想值的优化 EPL 载 NLCs 系统。优化后的 EPL 载 NLCs 系统的 PS 为 134nm，PDI 为 0.31，EE%（76±6.56%w/w）高，ZP（-32.37mV）。渗透研究表明，与水混悬液相比，24h 后兔肠中药物渗透增加了两倍，证实了优化的 EPL 载 NLCs 系统作为成功的口服靶向递药载体的能力。
我们的研究结果为 CSCR 治疗的新型口服纳米治疗方法铺平了道路。目前正在进行研究。
