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淀粉水凝胶作为靶向结肠给药载体

Starch hydrogels as targeted colonic drug delivery vehicles.

作者信息

Koev Todor T, Harris Hannah C, Kiamehr Sara, Khimyak Yaroslav Z, Warren Frederick J

机构信息

School of Pharmacy, University of East Anglia, Norwich Research Park, NR4 7TJ, UK; Food Innovation and Health, Quadram Institute Bioscience, Norwich Research Park, NR4 7UQ, UK.

Food Innovation and Health, Quadram Institute Bioscience, Norwich Research Park, NR4 7UQ, UK.

出版信息

Carbohydr Polym. 2022 Aug 1;289:119413. doi: 10.1016/j.carbpol.2022.119413. Epub 2022 Mar 26.

Abstract

Targeted colonic drug delivery systems are needed for the treatment of endemic colorectal pathologies, such as Crohn's disease, ulcerative colitis, and colorectal cancer. These drug delivery vehicles are difficult to formulate, as they need to remain structurally intact whilst navigating a wide range of physiological conditions across the upper gastrointestinal tract. In this work we show how starch hydrogel bulk structural and molecular level parameters influence their properties as drug delivery platforms. The in vitro protocols mimic in vivo conditions, accounting for physiological concentrations of gastrointestinal hydrolytic enzymes and salts. The structural changes starch gels undergo along the entire length of the human gastrointestinal tract have been quantified, and related to the materials' drug release kinetics for three different drug molecules, and interactions with the large intestinal microbiota. It has been demonstrated how one can modify their choice of starch in order to fine tune its corresponding hydrogel's pharmacokinetic profile.

摘要

治疗地方性结肠疾病,如克罗恩病、溃疡性结肠炎和结肠直肠癌,需要有针对性的结肠给药系统。这些药物递送载体难以配制,因为它们需要在整个上消化道的各种生理条件下保持结构完整。在这项工作中,我们展示了淀粉水凝胶的整体结构和分子水平参数如何影响其作为药物递送平台的性能。体外实验方案模拟体内条件,考虑了胃肠道水解酶和盐的生理浓度。已对淀粉凝胶在人类胃肠道全长范围内发生的结构变化进行了量化,并将其与三种不同药物分子的材料药物释放动力学以及与大肠微生物群的相互作用相关联。已经证明了如何通过改变淀粉的选择来微调其相应水凝胶的药代动力学特征。

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