Spray dried mebendazole–loaded Soluplus-based polymeric micelles for improved biopharmaceutical attributes: in vitro and in vivo studies

IF 2.2 4区化学 Q3 CHEMISTRY, PHYSICAL

Colloid and Polymer Science Pub Date : 2024-04-06 DOI:10.1007/s00396-024-05251-0

Tania Bajaj, Ghanshyam Das Gupta, Charan Singh

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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

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喷雾干燥的甲苯咪唑负载 Soluplus 聚合物胶束用于改善生物制药属性：体外和体内研究

摘要本研究旨在探讨喷雾干燥的甲苯咪唑（MBZ）负载 Soluplus 聚合物胶束（MBZ@PMs），以提高口服后的溶解度和生物吸收率。在制备 MBZ@PM 之后，使用傅立叶变换红外光谱、PXRD、DSC 和 TEM 技术对形成的胶束制剂进行了检测，以确定其物理和化学特性。临界胶束浓度测定研究表明，Soluplus® 能有效生成稳定的聚合物胶束。粒度分析表明，Soluplus® 呈球形，粒度为 538.7 ± 2.129 nm。溶解度研究表明，MBZ@PMs 在 pH 值为 6.8 的 PBS 中的溶解度比 MBZ 高约八倍（90.16 ± 2.54 µg/mL v/s 11.97 ± 2.99 µg/mL）。稳定性研究证实，制备的聚合物胶束的粒度分布和多分散指数变化微乎其微。体外释放研究表明，在 pH 值为 1.2 时，MBZ@PMs 的 MBZ 释放量较低（2 小时内释放 9.70 ± 3.2%），而在 PBS pH 值为 6.8 时，MBZ@PMs 的 MBZ 释放量在 48 小时内持续释放（33.3 ± 3.9%）。体内药代动力学研究表明，MBZ@PMs 的生物利用度（AUC0-ꝏ 153.81 ± 24.20 v/s 38.20 ± 5.55）高出约四倍，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作为一种潜在的载体系统，用于提高水溶性差的化合物的疗效。图表摘要

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来源期刊

Colloid and Polymer Science 化学-高分子科学

CiteScore

4.60

自引率

4.20%

发文量

111

审稿时长

2.2 months

期刊介绍： Colloid and Polymer Science - a leading international journal of longstanding tradition - is devoted to colloid and polymer science and its interdisciplinary interactions. As such, it responds to a demand which has lost none of its actuality as revealed in the trends of contemporary materials science.