A thermo-responsive chemically crosslinked long-term-release chitosan hydrogel system increases the efficiency of synergy chemo-immunotherapy in treating brain tumors

• Published in: International journal of biological macromolecules Vol. 280; no. Pt 3; p. 135894
• Main Authors: Chuang, Shun-Hao, Chen, Kuan-Ju, Cheng, Yu-Ting, Chen, Yu-Shuan, Lin, Shuian-Yin, Chou, Hsiao-Ying, Tsai, Hsieh-Chih
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2024
• Subjects: aldehydes; blood-brain barrier; brain; brain neoplasms; Brain tumor; Chemo-immunotherapy; chitosan; crosslinking; doxorubicin; drug therapy; glioblastoma; hydrogels; neoplasm progression; Thermo-responsive chitosan hydrogel; Brain tumor; Thermo-responsive chitosan hydrogel; Chemo-immunotherapy
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.135894

Glioblastoma multiforme (GBM) is an aggressive and common brain tumor. The blood-brain barrier prevents several treatments from reaching the tumor. This study proposes a Chemo-Immunotherapy synergy treatment chemically crosslinked hydrogel system that is injected into the tumor to treat GBM. The strategy uses doxorubicin and BMS-1 with a thermo-responsive and chemically crosslinked hydrogel for extended drug release into the affected area. The hydrogels are produced by mixing with Chitosan (Chi), modified Pluronic F-127 (PF-127) with aldehyde end group and doxorubicin and then chemically crosslinking the aldehyde and amine bonds to increase the drug retention time. PF-127-CHO/Chi, which gels at body temperatures and chemically crosslinks between PF-127-CHO and Chitosan, increases the time that the drug remains in the affected area and prevents the hydrogel from swelling and compressing surrounding tissue. The drug is released from the chemically crosslinked hydrogels, prevents tumor progression and increases survival for subjects with GBM tumors. The Synergy Chemo-Immunotherapy also allows more efficient treatment of GBM than chemotherapy. The PF-127-CHO/Chi DOX and BMS-1 group have a tumor that is 43 times smaller than the untreated group. These results show that the proposed chemically crosslinking hydrogel is an efficient intratumoral delivery platform for the treatment of tumors. Schematic illustration of the thermo-responsive, chemically crosslinked hydrogel system with chemoimmunotherapy (doxorubicin and BMS-1) to treat solid tumors. A Thermo-responsive Chemically Crosslinked Long-term-Release Chitosan Hydrogel System increases the Efficiency of Synergy Chemo-Immunotherapy in Treating Brain Tumors. The thermo-responsive chemically crosslinked hydrogel is injected after clinical surgery, crossing through the BBB and allows sustained release of drugs. Bioavailability is increased so combined synergy chemoimmunotherapy increases the efficiency for treating brain tumors. The hydrogel allows long-term delivery of a combination of anticancer therapeutics to treat a range of solid tumors. [Display omitted]