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

Hsiang-Kuang Tony Liang; Xue-Shi Lai; Ming-Feng Wei; Szu-Huai Lu; Wen-Fen Wen; Sung-Hsin Kuo; Chung-Ming Chen; Wen-Yih Isaac Tseng; Feng-Huei Lin

doi:10.1016/j.biomaterials.2017.10.015

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

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

Authors

Hsiang-Kuang Tony Liang¹, Xue-Shi Lai², Ming-Feng Wei³, Szu-Huai Lu³, Wen-Fen Wen⁴, Sung-Hsin Kuo⁵, Chung-Ming Chen², Wen-Yih Isaac Tseng⁶, Feng-Huei Lin⁷

Affiliations

¹ 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.
² Institute of Biomedical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan.
³ Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital: No. 7, Chung Shan South Rd., Zhongzheng Dist., Taipei 10002, Taiwan.
⁴ Department of Pathology, National Taiwan University Hospital, No. 7, Chung Shan South Rd., Zhongzheng Dist., Taipei 10002, Taiwan.
⁵ 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; Graduate Institute of Oncology, National Taiwan University College of Medicine: No. 1, Jen Ai Rd., Sec. 1, Zhongzheng Dist., Taipei 10051, Taiwan.
⁶ Institute of Medical Device and Imaging, National Taiwan University College of Medicine: No. 1, Jen Ai Rd. Sec. 1, Zhongzheng Dist., Taipei 10051, Taiwan.
⁷ Institute of Biomedical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan; Institute of Biomedical Engineering and Nano-medicine, National Health Research Institutes: No. 35, Keyan Rd., Zhunan Town, Miaoli County 35053, Taiwan. Electronic address: double@ntu.edu.tw.

PMID: 29059540
DOI: 10.1016/j.biomaterials.2017.10.015

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.

Keywords: Concurrent chemoradiotherapy; Intratumoral injection; Malignant glioma; Simplified drug delivery; Sustained-release carboplatin; Thermogelling hydrogel.

MeSH terms

3T3 Cells
Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / adverse effects
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Brain Neoplasms / drug therapy*
Brain Neoplasms / radiotherapy*
Carboplatin / administration & dosage
Carboplatin / adverse effects
Carboplatin / chemistry
Carboplatin / pharmacology*
Cell Line, Tumor
Cell Survival
Combined Modality Therapy
Delayed-Action Preparations
Drug Carriers / chemistry
Drug Liberation
Glioma / drug therapy*
Glioma / radiotherapy*
Humans
Hydrogels / chemistry*
Injections, Intralesional
Materials Testing / methods
Mice
Mice, Inbred C57BL
Tissue Distribution

Substances

Antineoplastic Agents
Delayed-Action Preparations
Drug Carriers
Hydrogels
Carboplatin