Dpto. de Ingeniería, Área Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández, Carretera Alicante-Valencia km. 87, 03550, San Juan, Alicante, Spain.
Instituto Mixto de Tecnología Química, Universidad Politécnica de Valencia-Consejo Superior de Investigaciones Científicas (UPV-CSIC), Avd. de los Naranjos s/n, 46006 Valencia, Spain.
Eur J Pharm Biopharm. 2019 Mar;136:174-183. doi: 10.1016/j.ejpb.2019.01.009. Epub 2019 Jan 14.
Hydrogels are widely studied as drug delivery system. In this work we propose the employment of tetrakis(hydroxymethyl)phosphonium chloride as crosslinking agent to obtain covalent hydrogels based on chitosan. These hydrogels are obtained by Mannich reaction between the amino groups of chitosan with the hydroxymethyl groups of the crosslinker molecule. They show a pH sensitive second order swelling kinetic, have low toxicity, are biocompatible, mucoadhesive and allow a modified release of the encapsulated drug, camptothecin, for 48 h. This antitumor drug has been studied as a drug of interest to develop oral chemotherapy administration strategies. According to the obtained results, oral administration of camptothecin through hydrogels would provide low concentrations of drug at the absorption site, avoiding carrier saturation and reducing its intestinal toxicity.
水凝胶作为药物传递系统被广泛研究。在这项工作中，我们提出使用四羟甲基氯化鏻作为交联剂，以获得基于壳聚糖的共价水凝胶。这些水凝胶是通过壳聚糖的氨基与交联剂分子的羟甲基之间的Mannich 反应获得的。它们表现出 pH 敏感的二级溶胀动力学，具有低毒性、生物相容性、粘膜粘附性，并允许封装药物喜树碱的释放时间延长至 48 小时。这种抗肿瘤药物已被研究作为开发口服化疗给药策略的候选药物。根据获得的结果，通过水凝胶口服给予喜树碱可以在吸收部位提供低浓度的药物，避免载体饱和并降低其肠道毒性。
