Triple-Tailored Analgesic Hydrogel System Targeting ADAM17 in Orofacial Inflammatory Pain.

Area of Science:

• Biomedical Engineering
• Pharmacology
• Pain Management

Background:

• Orofacial inflammatory pain (OFP) presents significant management challenges due to its complexity.
• Existing treatments often lack prolonged efficacy and targeted delivery for OFP.
• Identifying novel therapeutic targets is crucial for advancing OFP treatment.

Purpose of the Study:

• To develop a sustained-release drug delivery system for OFP management.
• To investigate ADAM17 as a therapeutic target for OFP.
• To create a customized hydrogel system for prolonged local drug delivery of TAPI-1.

Main Methods:

• Identification of ADAM17 as a therapeutic target for OFP and screening of its inhibitor, TAPI-1.
• Synthesis of a Schiff-base crosslinked hydrogel matrix using hyaluronic acid derivatives (HAALD) and aminated gelatin (AGel) for TAPI-1 encapsulation.
• Incorporation of unmodified hyaluronic acid and gelatin to optimize rheological properties for injection, and addition of hollow mesoporous silica nanoparticles to further prolong drug release.

Main Results:

• The developed triple-tailored hydrogel (HHGA hydrogel) successfully encapsulated TAPI-1.
• The HHGA hydrogel demonstrated sustained release of TAPI-1 for up to 7 days.
• Significant pain relief was observed in mice models treated with the HHGA hydrogel, correlating with the pain phase.

Conclusions:

• ADAM17 is a viable therapeutic target for OFP, with TAPI-1 showing inhibitory effects.
• The developed sustained-release HHGA hydrogel system provides prolonged drug delivery and effective pain management for OFP.
• This "drug-device" innovation highlights the potential of personalized medicine and targeted therapies in translational pain research.