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使用聚(甲基丙烯酸2-羟乙酯-共-丙烯酰胺)水凝胶进行5-氟尿嘧啶的体内药物递送。

In-vivo drug delivery of 5-fluorouracil using poly(2-hydroxyethyl methacrylate-co-acrylamide) hydrogels.

作者信息

Blanco M D, Garcia O, Gomez C, Sastre R L, Teijon J M

机构信息

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Spain.

出版信息

J Pharm Pharmacol. 2000 Nov;52(11):1319-25. doi: 10.1211/0022357001777469.

Abstract

Poly(2-hydroxyethyl methacrylate-co-acrylamide) hydrogels crosslinked with ethylen glycol dimethacrylate were used as devices for the in-vivo drug release of 5-fluorouracil (5-FU). Drug-loaded hydrogels were subcutaneously implanted in the back of Wistar rats. All hydrogel discs reached an equilibrium swelling degree, which was slightly larger than that determined in-vitro. After 30 days of implantation, the hydrogel discs were transparent, and without fracture or apparent degradation. In addition, a fibrous capsule was not detected around the hydrogels that had greater hydration degrees. Release of 5-FU from these hydrogels allows the drug to remain in the plasma from 1 to 5 days, in spite of its short plasma half-life (15 min). This was an improvement of up to 98-times compared with the intraperitoneal drug administration. Administration of 5-FU by implantation of 2-hydroxyethylmethacrylate-co-acrylamide copolymeric hydrogels seems to be a good candidate for 5-FU therapy, since the drug released results in a therapeutically suitable plasma concentration of 5-FU for an extended period of time, despite the short half-life of the drug.

摘要

用乙二醇二甲基丙烯酸酯交联的聚(甲基丙烯酸2-羟乙酯-共-丙烯酰胺)水凝胶被用作5-氟尿嘧啶(5-FU)体内药物释放的装置。将载药的水凝胶皮下植入Wistar大鼠的背部。所有水凝胶圆盘都达到了平衡溶胀度,该溶胀度略大于体外测定的值。植入30天后,水凝胶圆盘是透明的,没有断裂或明显降解。此外,在水合度较高的水凝胶周围未检测到纤维囊。尽管5-FU的血浆半衰期很短(15分钟),但从这些水凝胶中释放5-FU能使药物在血浆中保留1至5天。与腹腔内给药相比,这是高达98倍的改善。通过植入甲基丙烯酸2-羟乙酯-共-丙烯酰胺共聚物水凝胶来给药5-FU似乎是5-FU治疗的一个良好候选方法,因为尽管药物半衰期短,但释放的药物能在较长时间内产生治疗上合适的5-FU血浆浓度。

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