Simvastatin (SIM) is a HMG-CoA reductase inhibitor employed in the management of hyperlipidemia. However, its low bioavailability limits its clinical efficacy. The objective of this study was to overcome the poor bioavailability of SIM via the transdermal application of a SIM-loaded niosomal gel. Niosomes loaded with SIM were fabricated by means of the thin-film hydration method and optimized through a 3³-factorial design utilizing Design Expert^® software. The prepared niosomes were evaluated for entrapment efficiency (EE%), zeta potential, vesicle size, and cumulative percentage of drug release. The optimum niosomal formulation was loaded on the gel and evaluated for physical properties such as color, clarity, and homogeneity. It was also evaluated for spreadability, and the cumulative % drug release. The best niosomal gel formula was appraised for ex vivo permeation as well as pharmacokinetic study. The SIM-loaded niosomes showed EE% between 66.7–91.4%, vesicle size between 191.1–521.6 nm, and zeta potential ranged between −0.81–+35.6 mv. The cumulative percentage of drug released was ranged from 55% to 94% over 12 h. SIM-loaded niosomal gels were clear, homogenous, spreadable, and the pH values were within the range of physiological skin pH. Furthermore, about 73.5% of SIM was released within 24 h, whereas 409.5 µg/cm² of SIM passed through the skin over 24 h in the ex vivo permeation study. The pharmacokinetic study revealed higher AUC_0–∞ and Cmax with topical application of SIM-loaded niosomal gel compared to topical SIM gel or oral SIM suspension. The topical application of SIM-loaded niosomal gel ascertained the potential percutaneous delivery of SIM.

中文翻译：

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通过定制的Niosomal纳米囊泡制备和评估辛伐他汀用于增强透皮递送：体内和体内评估

辛伐他汀（SIM）是HMG-CoA还原酶抑制剂，用于高脂血症的治疗。但是，其低生物利用度限制了其临床疗效。这项研究的目的是通过透皮应用载有SIM的脂质体凝胶克服SIM较差的生物利用度。装有SIM囊泡是由薄膜水合方法制造和优化通过3 ³利用设计专家-factorial设计^®软件。评估制备的脂质体的包封率（EE％），ζ电势，囊泡大小和药物释放的累积百分比。将最佳的脂质体制剂加载到凝胶上，并评估其物理性质，例如颜色，透明度和均质性。还评估了其可铺展性和累积的药物释放百分比。评估了最佳的凝胶凝胶配方，可用于离体渗透以及药代动力学研究。载有SIM的纳米粒的EE％在66.7-91.4％之间，囊泡大小在191.1-521.6 nm之间，ζ电位在-0.81- + 35.6 mv之间。在12小时内，药物释放的累积百分比范围为55％至94％。装有SIM的脂质体凝胶清晰，均质，可铺展，pH值在皮肤生理pH范围内。此外，大约73。在离体渗透研究中，有²个SIM卡在24小时内通过了皮肤。药代动力学研究表明，与局部SIM凝胶或口服SIM悬浮液相比，局部应用SIM负载的基因组凝胶可提高AUC _0–∞和Cmax。载有SIM的染色体凝胶的局部应用可确定SIM的潜在经皮递送。