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Updated: Sep 16, 2025

The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications

The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications

Published on: October 7, 2016

Intelligently Actuating Dual-Barrier Hyaluronic Acid-Functionalized Inflammation-Responsive Nanohydrogel for Targeted

Raghuraj Singh^1,2, Hitesh Malhotra³, Krishna Jadhav¹

¹Institute of Nano Science and Technology (INST), Sector 81, Mohali, Punjab 140306, India.

ACS Applied Materials & Interfaces

|July 7, 2025

Summary

A novel nanohydrogel system delivers dexamethasone effectively for rheumatoid arthritis (RA) by targeting inflamed joints. This advanced drug delivery reduces inflammation and joint damage with fewer injections.

Keywords:

Dual-barrier Hydrogel Intelligently actuating Matrix metalloproteinases On-demand drug delivery Rheumatoid arthritis

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Area of Science:

Biomaterials Science
Nanotechnology
Rheumatology
Drug Delivery Systems

Background:

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint inflammation and damage.
Current intra-articular glucocorticoid treatments for RA have limitations including rapid clearance and systemic side effects.
Need for improved drug delivery strategies for sustained and targeted intra-articular therapy in RA.

Purpose of the Study:

To develop an inflammation-responsive, dual-barrier nanohydrogel system (Dex-LNP-HG) for sustained intra-articular dexamethasone (Dex) delivery.
To enhance therapeutic precision and reduce systemic exposure for rheumatoid arthritis treatment.
To overcome limitations of conventional glucocorticoid therapies in RA.

Main Methods:

Development of hyaluronic acid (HA)-functionalized dexamethasone-loaded lipid nanoparticles (Dex-LNPs) within a matrix metalloproteinase (MMP)-sensitive hydrogel.
The system utilizes enzyme-triggered degradation and CD44 receptor-mediated uptake by activated macrophages.
Evaluation in preclinical rheumatoid arthritis models.

Main Results:

A single intra-articular injection of Dex-LNP-HG significantly reduced synovial inflammation (6.5-fold) and joint damage (7-fold) in RA models.
The nanohydrogel system demonstrated sustained drug release, avoiding burst release and improving drug localization.
Reduced injection frequency and enhanced therapeutic efficacy compared to conventional methods.

Conclusions:

The Dex-LNP-HG nanohydrogel system offers a promising strategy for sustained and targeted intra-articular dexamethasone delivery in rheumatoid arthritis.
This dual-triggered system improves efficacy, safety, and patient compliance by addressing key limitations of current RA therapies.
The integration of HA and MMP-sensitive hydrogels represents an advancement in nanotherapeutic approaches for autoimmune joint diseases.