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载有 5-氟尿嘧啶的可生物降解三维微器件在荷瘤小鼠中的应用。

Biodegradable three-dimension micro-device delivering 5-fluorouracil in tumor bearing mice.

机构信息

School of Medicine, Xi'an Jiaotong University, Xi'an 710061, PR China.

出版信息

Drug Deliv. 2012 Jan;19(1):36-44. doi: 10.3109/10717544.2011.635720.

Abstract

A novel three-dimension micro-device was formulated to control delivery of 5-fluorouracil (5-FU) for the treatment of solid tumors. The poly-(lactic-co-glycolic) acid (PLGA), which is both biocompatible and biodegradable, was used as carrier material. The characteristics of drug release in vitro and in vivo and the performance of the micro-device after implantation in tumor bearing mice were evaluated. A constant release profile from in vitro test was obtained for a period of 7 days, and it correlated well with the in vivo release profile. In the distribution experiment of 5-FU micro-device, it was demonstrated that 5-FU remained in the tumor tissues for more than 7 days after implantation. Likewise, we found that the 5-FU concentration in tumor correlated well with the in vivo release. Tumors treated with 5-FU loaded micro-device of three different dosages showed significant tumor reduction (P < 0.05) compared with empty control micro-device 7 days after administration. Moreover, the implantation treatment showed enhanced efficacy compared with the intraperitoneal administration with the same dosage. These results suggested that the three-dimensional micro-device may provide a promising local and controlled release drug delivery system, which may enable delivery of multiple drugs for post-surgical chemotherapy against solid tumor.

摘要

一种新型的三维微器件被构建用于控制 5-氟尿嘧啶(5-FU)的递送,以治疗实体瘤。聚(乳酸-共-乙醇酸)(PLGA)作为载体材料,具有生物相容性和可生物降解性。评估了体外和体内药物释放的特征以及植入荷瘤小鼠后的微器件的性能。体外试验获得了长达 7 天的恒定释放曲线,与体内释放曲线具有良好的相关性。在 5-FU 微器件的分布实验中,证明了植入后 5-FU 在肿瘤组织中保留了超过 7 天。同样,我们发现肿瘤中的 5-FU 浓度与体内释放具有良好的相关性。与空载体微器件相比,三种不同剂量的负载 5-FU 的微器件治疗后 7 天肿瘤明显缩小(P<0.05)。此外,与相同剂量的腹腔内给药相比,植入治疗显示出增强的疗效。这些结果表明,三维微器件可能提供一种有前途的局部和控制释放药物递送系统,可用于递送多种药物进行术后化疗以对抗实体瘤。

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