Drug Research Program, Division of Pharmaceutical Chemistry Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, 90110, Hat Yai, Thailand.
Adv Healthc Mater. 2017 Oct;6(20). doi: 10.1002/adhm.201700629. Epub 2017 Jul 17.
An advanced oral drug delivery system that can effectively deliver drugs with poor oral bioavailability is strongly desirable. Herein, a multifunctional nano-in-micro structured composite is developed by encapsulation of the mucoadhesive poly(methyl vinyl ether-co-maleic acid) modified halloysite nanotubes (HNTs) with the pH-responsive hydroxypropyl methylcellulose acetate succinate by the microfluidics to control the drug release, increase cell-particle interaction, and improve drug absorption. The microparticles show spherical shape, homogeneous particle size distribution (58 ± 1 µm), and pH-responsive dissolution behavior at pH > 6, and they prevent the premature release of curcumin in simulated pH conditions of the stomach and immediately release the curcumin in simulated pH conditions of the small intestine. The surface modification of HNT with mucoadhesive poly(methyl vinyl ether-co-maleic acid) significantly enhances its interactions with the intestinal Caco-2/HT29-MTX cells and the mouse small intestines, and increases the permeability of curcumin across the co-cultured Caco-2/HT29-MTX cell monolayers by about 13 times compared to the free curcumin. Therefore, the developed multifunctional nanotube-mucoadhesive poly(methyl vinyl ether-co-maleic acid)@hydroxypropyl methylcellulose acetate succinate composite is a promising oral drug delivery system for drugs with poor oral bioavailability.
一种先进的口服药物传递系统，能够有效地传递生物利用度差的药物，是非常需要的。本文通过微流控技术将具有 pH 响应性的羟丙甲纤维素醋酸琥珀酸酯包裹在具有黏膜黏附性的聚甲基乙烯基醚-马来酸（poly(methyl vinyl ether-co-maleic acid)）改性的埃洛石纳米管（HNTs）中，开发了一种多功能纳米-微结构复合体系，以控制药物释放、增加细胞-颗粒相互作用、提高药物吸收。该微球呈球形，具有均匀的粒径分布（58 ± 1 µm），在 pH > 6 时具有 pH 响应性的溶解行为，能够防止姜黄素在模拟胃环境中的过早释放，并在模拟小肠环境的 pH 条件下立即释放姜黄素。HNT 的黏膜黏附性聚甲基乙烯基醚-马来酸（poly(methyl vinyl ether-co-maleic acid)）表面改性显著增强了其与肠道 Caco-2/HT29-MTX 细胞和小鼠小肠的相互作用，并使姜黄素穿过共培养的 Caco-2/HT29-MTX 细胞单层的通透性增加了约 13 倍，与游离姜黄素相比。因此，开发的多功能纳米管-黏膜黏附性聚甲基乙烯基醚-马来酸（poly(methyl vinyl ether-co-maleic acid)）@羟丙甲纤维素醋酸琥珀酸酯复合体系是一种有前途的用于生物利用度差的口服药物的传递系统。
