Electrically controlled hyaluronic acid-based hydrogel for sustained and repeatable metronomic chemotherapy

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Oncology

Background:

• Metronomic chemotherapy requires sustained drug levels but faces challenges in dose control and patient compliance.
• Existing electro-responsive drug delivery systems have limitations in clinical applicability due to biodegradability, cytotoxicity, or manufacturing complexity.

Purpose of the Study:

• To develop a biocompatible, biodegradable, and electro-responsive hydrogel (HTZ@D) for precise, on-demand delivery of doxorubicin (DOX).
• To evaluate the efficacy and safety of HTZ@D in vitro and in vivo for metronomic chemotherapy.

Main Methods:

• HTZ@D hydrogel synthesized using hyaluronic acid, tannic acid, and zinc ions, loaded with DOX, and cross-linked with BDDE.
• Electro-responsive drug release triggered by low-voltage AC stimulation (6 Vpp, 500 kHz).
• In vitro and in vivo studies to assess drug release kinetics, cytotoxicity, anti-tumor efficacy, and systemic toxicity.

Main Results:

• HTZ@D demonstrated programmable DOX release for over 14 days with minimal passive leakage.
• In vitro studies showed selective tumor cell death under stimulation with low toxicity to fibroblasts.
• In vivo studies significantly inhibited tumor growth, modulated the tumor microenvironment, and showed no systemic toxicity.

Conclusions:

• HTZ@D is a clinically transferable platform overcoming limitations of conventional chemotherapy.
• The system offers scalable manufacturing, on-demand dosing, and immunomodulatory effects for precision oncology.
• This advancement holds significant potential for programmable drug delivery and improved cancer treatment strategies.