# A Study on the Treatment of Rheumatoid Arthritis Using a Novel GelMA-HAMA Dual-Network Hydrogel Microneedle Loaded with MTX-NCs in Combination with Adalimumab

## TL;DR

A new hydrogel microneedle patch was developed to deliver drugs for rheumatoid arthritis, offering a painless and effective treatment option.

## Contribution

A novel dual-network hydrogel microneedle patch loaded with methotrexate nanocrystals was developed for transdermal RA treatment.

## Key findings

- The MTX-NCs had a spherical shape, average size of 325.72 nm, and 61.3% drug-loading capacity.
- The microneedle patch showed high puncture efficiency and strong anti-inflammatory effects in vitro and in vivo.
- Combination therapy with Adalimumab enhanced the anti-inflammatory efficacy and reduced joint damage in a rat RA model.

## Abstract

This study developed a transdermal drug delivery system for Rheumatoid Arthritis (RA) using a dual-network hydrogel microneedle patch loaded with methotrexate nanocrystals (DHMN@MTX-NCs), and explored its synergistic therapy with Adalimumab (ADA) for a painless, long-acting, and targeted RA treatment. This study synthesized Methacrylated Hyaluronic Acid and Methacrylated Gelatin. MTX-NCs were prepared by solvent-antisolvent precipitation and incorporated into a dual-network hydrogel microneedle patch via centrifugal molding. Evaluations included pharmaceutical properties, mechanical strength, drug release, in vitro anti-inflammatory effects on RAW 264.7 cells, and therapeutic efficacy in a rat RA model. The experimental results show that the prepared MTX-NCs present a spherical shape, an average size of 325.72 nm, a PDI of 0.154, and a drug-loading capacity of 61.3%. The microneedle patch exhibited high puncture efficiency and suitable swelling. In vitro, DHMN@MTX-NCs combined with ADA most strongly inhibited macrophage migration, upregulated IL-10, and downregulated TNF-α, IL-1β, NO, iNOS, and COX-2. In vivo, both monotherapy and combination therapy reduced joint swelling, bone erosion, and histopathological damage. Ultimately, the study demonstrated the synergistic anti-inflammatory efficacy of DHMN@MTX-NCs combined with ADA, providing a novel, non-invasive, and targeted therapeutic strategy for RA.