Methotrexate, which is widely used in the treatment of cancer and immune-related diseases, has limitations in use because of its low bioavailability, short half-life, and tissue toxicity. Thus, in this study, a nano-sized water-in-oil-in-water (W/O/W) double emulsion containing methotrexate was prepared to enhance its lymphatic delivery and bioavailability. Based on the results from solubility testing and a pseudo-ternary diagram study, olive oil as the oil, Labrasol as a surfactant, and ethanol as a co-surfactant, were selected as the optimal components for the nanoemulsion. The prepared nanoemulsion was evaluated for size, zeta potential, encapsulation efficiency, pH, morphology, and in vitro release profiles. Furthermore, pharmacokinetics and lymphatic targeting efficiency were assessed after oral and intravenous administration of methotrexate-loaded nanoemulsion to rats. Mean droplet size, zeta potential, encapsulation efficiency, and pH of formulated nanoemulsion were 173.77 ± 5.76 nm, −35.63 ± 0.78 mV, 90.37 ± 0.96%, and 4.07 ± 0.03, respectively. In vitro release profile of the formulation indicated a higher dissolution and faster rate of methotrexate than that of free drug. The prepared nanoemulsion showed significant increases in maximum plasma concentration, area under the plasma concentration-time curve, half-life, oral bioavailability, and lymphatic targeting efficiency in both oral and intravenous administration. Therefore, our research proposes a methotrexate-loaded nanoemulsion as a good candidate for enhancing targeted lymphatic delivery of methotrexate.

中文翻译：

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使用W / O / W纳米乳剂增强甲氨蝶呤的淋巴递送：体外表征和药代动力学研究

甲氨蝶呤由于其生物利用度低，半衰期短和组织毒性小，因此在使用中存在局限性，广泛用于治疗癌症和免疫相关疾病。因此，在这项研究中，制备了含有甲氨蝶呤的纳米尺寸的水包水包油型（W / O / W）双重乳液，以增强其淋巴输送和生物利用度。根据溶解度测试和伪三元图研究的结果，选择橄榄油作为油，Labrasol作为表面活性剂和乙醇作为辅助表面活性剂，作为纳米乳液的最佳组分。评价制备的纳米乳剂的尺寸，ζ电位，包封效率，pH，形态和体外释放曲线。此外，在口服和静脉内施用甲氨蝶呤纳米乳剂后，评估了药代动力学和淋巴靶向效率。配制的纳米乳剂的平均液滴尺寸，ζ电位，包封效率和pH分别为173.77±5.76nm，-35.63±0.78mV，90.37±0.96％和4.07±0.03。制剂的体外释放曲线表明，与游离药物相比，甲氨蝶呤的溶出度更高，甲氨蝶呤的释放速度更快。制备的纳米乳剂在口服和静脉内给药中均显示最大血浆浓度，血浆浓度-时间曲线下面积，半衰期，口服生物利用度和淋巴靶定效率显着增加。因此，