The current study aimed to encapsulate fluvastatin sodium (FVS), a member of the statins family possessing pleiotropic effects in rheumatoid arthritis (RA), into spanlastic nanovesicles (SNVs) for transdermal delivery. This novel delivery could surmount FVS associated oral encumbrances such as apparent first-pass effect, poor bioavailability and short elimination half-life, hence, accomplishing platform for management of RA. To consummate this objective, FVS-loaded SNVs were elaborated by thin film hydration method, utilizing either Span 60 or Span 80, together with Tween 80 or Brij 35 as an edge activator according to full factorial design (24). Applying Design-Expert® software, the influence of formulation variables on SNVs physicochemical properties and the optimized formulation selection were explored. Additionally, the pharmacokinetic studies were scrutinized in rats. Furthermore, in Freund's adjuvant-induced arthritis, rheumatoid markers, TNF-α, IL-10, p38 MAPK, and antioxidant parameters were measured. The optimum SNVs were nano-scaled spherical vesicles (201.54 ± 9.16 nm), having reasonable entrapment efficiency (71.28 ± 2.05%), appropriate release over 8 h (89.45 ± 3.64%) and adequate permeation characteristics across the skin (402.55 ± 27.48 µg/cm2). The pharmacokinetic study disclosed ameliorated bioavailability of the optimum SNVs gel by 2.79- and 4.59-fold as compared to the oral solution as well as the traditional gel, respectively. Moreover, it elicited a significant suppression of p38 MAPK expression and also significant improvement of all other measured biomarkers. Concisely, the foregoing findings proposed that SNVs can be auspicious for augmenting FVS transdermal delivery for management of RA.

中文翻译：

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通过定制的弹力纳米囊泡透皮递送氟伐他汀钠：通过抑制p38 MAPK信号通路减轻了弗氏佐剂诱导的大鼠类风湿关节炎。

目前的研究旨在将氟伐他汀钠（FVS）（一种在风湿性关节炎（RA）中具有多效性的他汀类药物的一种）封装到跨弹性纳米囊泡（SNV）中，以进行透皮递送。这种新颖的给药方式可以克服FVS相关的口服障碍，例如明显的首过效应，不良的生物利用度和较短的消除半衰期，从而为RA的治疗提供了理想的平台。为了达到这个目的，根据全析因设计，采用Span 60或Span 80以及Tween 80或Brij 35作为边缘活化剂，通过薄膜水化方法对FVS负载的SNV进行了细化。应用Design-Expert®软件，研究了配方变量对SNVs理化性质的影响以及优化的配方选择。此外，仔细研究了大鼠的药代动力学研究。此外，在弗氏佐剂诱发的关节炎中，测量了类风湿标志物，TNF-α，IL-10，p38 MAPK和抗氧化剂参数。最佳的SNV是纳米级球形囊泡（201.54±9.16 nm），具有合理的包封率（71.28±2.05％），在8小时内适当释放（89.45±3.64％），并且在皮肤上具有足够的渗透性（402.55±27.48 µg） / cm2）。药代动力学研究表明，与口服溶液和传统凝胶相比，最佳SNVs凝胶的生物利用度分别降低了2.79和4.59倍。此外，它引起p38 MAPK表达的显着抑制，并且所有其他测得的生物标志物也显着改善。简而言之，