瘤内注射温敏性和持续释放卡铂水凝胶，简化了给药方式，并保持了与放疗对小鼠脑胶质瘤的协同作用。

Intratumoral injection of thermogelling and sustained-release carboplatin-loaded hydrogel simplifies the administration and remains the synergistic effect with radiotherapy for mice gliomas.

机构信息

Institute of Biomedical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan; Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital: No. 7, Chung Shan South Rd., Zhongzheng Dist., Taipei 10002, Taiwan; Radiation Science and Proton Therapy Center, National Taiwan University College of Medicine, No. 7, Chung Shan South Rd., Zhongzheng Dist., Taipei 10002, Taiwan; Department of Neurology, National Taiwan University Hospital, No. 7, Chung Shan South Rd., Zhongzheng Dist., Taipei 10002, Taiwan.

Institute of Biomedical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan.

出版信息

Biomaterials. 2018 Jan;151:38-52. doi: 10.1016/j.biomaterials.2017.10.015. Epub 2017 Oct 9.

DOI:10.1016/j.biomaterials.2017.10.015

PMID:29059540

Abstract

BACKGROUND

Carboplatin, an antineoplastic agent, binds DNA and enhances radiotherapy (RT) effects. Carboplatin-loaded hydrogel (oxidized hyaluronic acid/adipic acid dihydrazide) enables the sustained drug release and facilitates the synergistic effect with RT.

PURPOSE

We investigated the effectiveness and convenience of hydrogel carboplatin combined with RT for mice glioma.

MATERIALS AND METHODS

Mouse glioma cells (ALTS1C1) were subcutaneously implanted in the right thigh of C57BL/6 mice on Day 0. The mice were categorized by treatments: sham, hydrogel, hydrogel carboplatin, aqueous carboplatin, RT, hydrogel carboplatin/RT, and aqueous carboplatin/RT. Hydrogel carboplatin (300 μg single dose on Day 7) or aqueous carboplatin (100 μg daily dose on Days 7, 8, and 9) was administered via intratumoral injection. RT was delivered a daily dose of 10 Gy on Days 8 and 9.

RESULTS

For mice administered hydrogel carboplatin/RT versus those administered aqueous carboplatin/RT, the 24-day tumor growth control rate and 104-day recurrence-free survival rate were 100% and 50% versus 100% and 66.7% (p = 0.648), respectively. However, mice receiving other treatments showed tumor progression by Day 24 and died within 40 days of tumor cell implantation.

CONCLUSIONS

Hydrogel carboplatin simplified intratumoral drug delivery and remained the synergistic effects with RT, which is potential for clinical applications.

摘要

背景

顺铂是一种抗肿瘤药物，可与 DNA 结合并增强放射治疗（RT）的效果。载顺铂水凝胶（氧化透明质酸/己二酸二酰肼）可实现药物的持续释放，并促进与 RT 的协同作用。

目的

我们研究了水凝胶顺铂联合 RT 治疗小鼠脑胶质瘤的疗效和便利性。

材料与方法

于第 0 天在 C57BL/6 小鼠右侧大腿皮下植入小鼠脑胶质瘤细胞（ALTS1C1）。根据治疗方法将小鼠分为：假手术组、水凝胶组、水凝胶顺铂组、顺铂水溶液组、RT 组、水凝胶顺铂/RT 组和顺铂水溶液/RT 组。水凝胶顺铂（第 7 天单次 300μg）或顺铂水溶液（第 7、8 和 9 天每日 100μg）通过瘤内注射给药。第 8 和 9 天给予 RT 每日 10Gy 剂量。