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Ascorbyl Palmitate Hydrogel for Local Intestinal Delivery of Macromolecules

机译:棕榈酸抗坏血酸酯水凝胶用于大分子的局部肠道递送

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摘要

Biologics have changed the management of inflammatory bowel disease (IBD), but there are concerns with unexpected systemic toxicity and loss of therapeutic response following administration by injection. Rectal administration of biologics offers potentially reduced therapy costs, as well as safer and more effective local delivery to inflammation sites. Hydrogels are potentially useful carriers of biologics for improved delivery to the inflamed intestinal mucosa. Here, we prepared a hydrogel system based on ascorbyl palmitate (AP) and incorporated a model macromolecular drug (fluorescently-labelled dextran) into the system. Characterization of gel properties included rheology, drug loading and release, cytotoxicity, and drug delivery in an in vitro intestinal model. We report that this hydrogel can be formed under a moderate environment that is amenable to incorporation of some biologics. The system showed a shear-thinning behavior. AP hydrogel released approximately 60% of the drug within 5 h and showed reasonable a cytotoxicity profile. The study therefore provides evidence that AP hydrogel has potential for local delivery of macromolecules to the intestinal mucosa in IBD.
机译:生物制剂已改变了炎症性肠病(IBD)的治疗方法,但存在注射给药后意外的全身毒性和失去治疗反应的担忧。直肠给药生物制剂可以潜在地降低治疗成本,以及更安全,更有效地局部递送至炎症部位。水凝胶是潜在的有用的生物制剂载体,用于改善向发炎的肠粘膜的递送。在这里,我们准备了一个基于抗坏血酸棕榈酸酯(AP)的水凝胶系统,并将模型高分子药物(荧光标记的右旋糖酐)掺入该系统中。凝胶特性的表征包括体外肠模型中的流变学,药物负载和释放,细胞毒性和药物递送。我们报告说,这种水凝胶可以在适合某些生物制剂掺入的适度环境下形成。该系统显示出剪切稀化行为。 AP水凝胶在5小时内释放了约60%的药物,并显示出合理的细胞毒性谱。因此,该研究提供了证据,表明AP水凝胶具有将大分子局部递送至IBD肠粘膜的潜力。

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