Modified chitosan thermosensitive hydrogel enables sustained and efficient anti-tumor therapy via intratumoral injection
Modified chitosan thermosensitive hydrogel enables sustained and efficient anti-tumor therapy via intratumoral injection
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改性壳聚糖热敏水凝胶可通过瘤内注射实现持续有效的抗肿瘤治疗
DOI：
10.1016/j.carbpol.2016.02.059
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发表时间：
2016-06-25
影响因子：
11.2
通讯作者：
Qi, Xiaole
中科院分区：
文献类型：
--
作者：
Jiang, Yingchun;Meng, Xuanyu;Qi, Xiaole
温敏性原位水凝胶是实现肿瘤内给药的潜在候选材料，但其机械强度较弱，往往导致严重的药物泄漏和爆裂。本文以壳聚糖为基质，经戊二醛（GA）和聚乙烯醇（PVA）改性，制备了一种具有高机械强度的温敏性水凝胶，用于紫杉醇（PTX）的瘤内给药。改性后的水凝胶体系可以在35.79 +/- 0.4 ℃下实现溶胶-凝胶转变，并表现出比简单壳聚糖水凝胶高7.03倍的机械强度。此外，发现负载PTX的改性水凝胶在PBS（pH 7.4）中的药物释放延长至13天。在荷H22肿瘤的小鼠中瘤内给药后，与Taxol（R）相比，装载PTX的改性水凝胶显示出3.72倍的抗肿瘤活性。总之，这些改性的水凝胶系统被证明是一种有前途的方式，以实现有效的持续释放和增强的抗肿瘤治疗效率的抗癌药物，通过原位肿瘤注射给药。(C)2016爱思唯尔有限公司版权所有。
Thermosensitive in situ hydrogels are potential candidates to achieve intratumoral administration, nevertheless their weak mechanical strength always lead to serious drug leakage and burst. Herein, we developed a chitosan based thermosensitive hydrogel of high mechanical strength, which was modified by glutaraldehyde (GA) and polyvinyl alcohol (PVA), for intratumoral delivery of paclitaxel (PTX). The modified hydrogel system could achieve sol-gel transition at 35.79 +/- 0.4 degrees C and exhibit a 7.03-fold greater mechanical strength compared with simple chitosan hydrogel. Moreover, the drug release of PTX loaded modified hydrogel in PBS (pH 7.4) was found to be extended to 13 days. After intratumoral administration in mice bearing H22 tumors, PTX-loaded modified hydrogels exhibited a 3.72-fold greater antitumor activity compared with Taxol (R). Overall, these modified hydrogel systems demonstrated to be a promising way to achieve efficient sustained release and enhanced anti-tumor therapy efficiency of anticancer drugs through in situ tumor injectable administration. (C) 2016 Elsevier Ltd. All rights reserved.