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Biomaterials ; 151: 38-52, 2018 Jan.
Article in English | MEDLINE | ID: mdl-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.


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