Sulfamethazine-based pH-sensitive hydrogels with potential application for transcatheter arterial chemoembolization...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Oncology

Background:

• Transcatheter arterial chemoembolization (TACE) is a common palliative treatment for unresectable hepatocellular carcinoma (HCC).
• Conventional TACE using Lipiodol® emulsions faces limitations in drug concentration stability and controlled release.
• There is a need for improved embolic materials for more effective HCC treatment.

Purpose of the Study:

• To develop a novel pH-sensitive, radiopaque block copolymer for TACE.
• To evaluate the copolymer's sol-to-gel transition, drug release kinetics, and in vivo performance.
• To enhance drug delivery and therapeutic efficacy in HCC treatment.

Main Methods:

• Fabrication of a sulfamethazine-based anionic pH-sensitive block copolymer (PCL-PEG-SM) via free radical polymerization.
• Assessment of the copolymer's sol-to-gel phase transition in response to pH changes (pH 7.4 to 6.5-7.0) at 37°C.
• In vitro evaluation of doxorubicin (DOX) release from hydrogels and its anti-cancer activity.
• In vivo study using a rabbit VX2 carcinoma hepatic tumor model to assess radiopaque embolic formulation gelation after intraarterial administration.

Main Results:

• The PCL-PEG-SM copolymer demonstrated a pH-sensitive sol-to-gel transition, forming a gel at tumor-relevant pH conditions.
• Sustained release of doxorubicin (DOX) from the hydrogels for over 4 weeks in vitro, with retained bioactivity against hepatic cancer cells.
• Radiopaque embolic formulations successfully gelled within the tumor after administration in a rabbit HCC model.
• The developed material shows potential as an injectable, radiopaque liquid embolic solution for TACE.

Conclusions:

• A novel anionic pH-sensitive block copolymer (PCL-PEG-SM) was successfully developed for TACE applications.
• The material exhibits desirable properties including injectability, pH-triggered gelation, sustained drug release, and radiopacity.
• This innovative embolic solution holds significant promise for improving the efficacy of TACE in treating hepatocellular carcinoma.