Plumbagin, a potential bioactive lipophilic molecule, possesses limited solubility and low oral bioavailability. The purpose of the present study was to examine the potential of the self-nanoemulsifying drug delivery system for improving solubility and oral bioavailability of plumbagin. The self-nanoemulsifying drug delivery system was formulated from Capmul MCM (oil), Tween 20 (surfactant), and propylene glycol (cosurfactant). Central composite design was employed as statistical tool to optimize the formulation variables, X1 (oil) and X2 (surfactant: co-surfactant mixture ratio), of the self-nanoemulsifying drug delivery system. The responses studied were droplet size, self-emulsification time, % of drug release in 15 min, and equilibrium solubility. The optimized liquid self-nanoemulsifying drug delivery system was adsorbed on Neusilin US2 and characterized for flow properties, X-ray diffractometry, differential scanning calorimetry, in vitro dissolution, in vivo anti-inflammatory activity, and bioavailability study in Wistar rats, as well as ex vivo permeation study. The droplet size, polydispersity index, self-emulsification time, and equilibrium solubility of the optimized formulation were 58.500 ± 1.170 nm, 0.228 ± 0.012, 17.660 ± 1.520 s, and 34.180 ± 1.380 mg/mL, respectively. Its zeta potential, transmittance value, and cloud point were - 28.200 ± 1.200 mV, 99.200% ± 0.600, and 90 °C, respectively. Drug release was found to be 93.320% ± 1.090. In vivo anti-inflammatory study confirmed more enhanced activity from the self-nanoemulsifying drug delivery system than with pure plumbagin. Pharmacokinetic study in rats revealed that solid self-nanoemulsifying drug delivery system had 4.49-fold higher bioavailability than pure plumbagin. Ex vivo permeation study demonstrated 1.75-fold increased intestinal permeability of the self-nanoemulsifying drug delivery system than pure plumbagin. The developed self-nanoemulsifying drug delivery system is a useful solid platform for improving solubility and oral bioavailability of plumbagin.

中文翻译：

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自纳米乳化给药系统的优化与评价以提高白花心苷的生物利用度

Plumbagin 是一种潜在的生物活性亲脂性分子，具有有限的溶解度和低的口服生物利用度。本研究的目的是检验自纳米乳化给药系统在改善白花丹素的溶解度和口服生物利用度方面的潜力。自纳米乳化给药系统由 Capmul MCM（油）、吐温 20（表面活性剂）和丙二醇（辅助表面活性剂）配制而成。采用中心复合设计作为统计工具来优化自纳米乳化给药系统的配方变量 X1（油）和 X2（表面活性剂：辅助表面活性剂混合比）。研究的响应是液滴大小、自乳化时间、15 分钟内药物释放的百分比和平衡溶解度。将优化的液体自纳米乳化给药系统吸附在 Neusilin US2 上，并对其流动特性、X 射线衍射、差示扫描量热法、体外溶出度、体内抗炎活性和 Wistar 大鼠的生物利用度进行了表征，以及离体渗透研究。优化配方的液滴大小、多分散指数、自乳化时间和平衡溶解度分别为 58.500 ± 1.170 nm、0.228 ± 0.012、17.660 ± 1.520 s 和 34.180 ± 1.380 mg/mL。其 zeta 电位、透射率值和浊点分别为 - 28.200 ± 1.200 mV、99.200% ± 0.600 和 90 °C。发现药物释放为 93.320% ± 1.090。体内抗炎研究证实，自纳米乳化药物递送系统的活性比纯白花青素更强。大鼠药代动力学研究表明，固体自纳米乳化给药系统的生物利用度比纯白花丹素高 4.49 倍。体外渗透研究表明，自纳米乳化药物递送系统的肠道通透性比纯白花菊素增加 1.75 倍。开发的自纳米乳化给药系统是一个有用的固体平台，用于提高白花心素的溶解度和口服生物利用度。