Abstract

The aim of this research was to investigate spray-dried mebendazole (MBZ)–loaded Soluplus-based polymeric micelles (MBZ@PMs) for improved solubility and bioabsorption upon oral administration. Following the MBZ@PM preparation, the formed micellar preparation was examined using FTIR, PXRD, DSC, and TEM techniques to determine its physical and chemical properties. Critical micelle concentration determination studies showed that Soluplus® can effectively generate stable polymeric micelles. Particle size analysis demonstrated spherical shape and a particle size of 538.7 ± 2.129 nm. Solubility studies demonstrated approximately eight times higher solubility of MBZ@PMs vis-à-vis MBZ in PBS pH 6.8 (90.16 ± 2.54 µg/mL v/s 11.97 ± 2.99 µg/mL). Stability studies confirmed that the size distribution and polydispersity index of the prepared polymeric micelles showed negligible variations. In vitro release studies revealed low MBZ release from MBZ@PMs (9.70 ± 3.2% in 2 h) at pH 1.2 and sustained (33.3 ± 3.9%) at PBS pH 6.8 in 48 h. In vivo pharmacokinetic studies showed approximately fourfold higher bioavailability (AUC_0-ꝏ 153.81 ± 24.20 v/s 38.20 ± 5.55) and 1.5-fold extended half-life of MBZ from MBZ@PMs (2.13 ± 0.53 v/s 1.44 ± 0.36). Therefore, these unprecedented Soluplus®-based polymeric micelles of Mebendazole can be applied as a potential carrier system to improve the therapeutic efficacy of poorly water-soluble compounds.

Graphical Abstract

中文翻译：

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喷雾干燥的装载甲苯咪唑的基于 Soluplus 的聚合物胶束可改善生物制药属性：体外和体内研究

摘要

本研究的目的是研究喷雾干燥的甲苯咪唑 (MBZ) 负载的基于 Soluplus 的聚合物胶束 (MBZ@PMs)，以提高口服给药时的溶解度和生物吸收。 MBZ@PM 制备后，使用 FTIR、PXRD、DSC 和 TEM 技术检查形成的胶束制剂，以确定其物理和化学性质。临界胶束浓度测定研究表明Soluplus®可以有效生成稳定的聚合物胶束。粒度分析表明其形状为球形，粒度为 538.7 ± 2.129 nm。溶解度研究表明，MBZ@PMs 在 PBS pH 6.8 中的溶解度大约是MBZ的八倍（90.16 ± 2.54 µg/mL vs 11.97 ± 2.99 µg/mL）。稳定性研究证实，所制备的聚合物胶束的尺寸分布和多分散指数的变化可以忽略不计。体外释放研究表明，在 pH 1.2 下，MBZ@PM 的 MBZ 释放量较低（2 小时内 9.70 ± 3.2%），在 PBS pH 6.8 下 48 小时内持续释放（33.3 ± 3.9%）。体内药代动力学研究表明，MBZ@PM 的生物利用度提高了约四倍（AUC _0-ꝏ 153.81 ± 24.20 v/s 38.20 ± 5.55），MBZ 半衰期延长了 1.5 倍（2.13 ± 0.53 v/s 1.44 ± 0.36）。因此，这些前所未有的基于Soluplus®的甲苯咪唑聚合物胶束可以作为潜在的载体系统来提高难溶性化合物的治疗效果。

图形概要