pH-responsive microneedle patches based on poly(dextran-co-methacrylic acid) hydrogels for controlled drug release.

Abstract

This study reports the synthesis, characterization, and biological evaluation of pH-responsive dextran-based hydrogel microneedles (MNs) for controlled drug delivery. Dextran (Dex) was chemically modified with glycidyl methacrylate (GMA) to obtain dextran methacrylate (DexMA), which was copolymerized with methacrylic acid (MAA) via free-radical polymerization to produce poly(DexMA-co-MAA) hydrogels with different compositions. The successful modification of Dex and copolymer formation were confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H NMR), thermogravimetric analyses (TGA), and scanning electron microscopy (SEM). The hydrogels exhibited pH-responsive swelling behavior, influenced by the DexMA:MAA ratio. Hydrogel-based MNs patches were fabricated using micromolding, producing well-defined pyramidal structures (450 μm × 200 μm). Doxorubicin (DOX) was incorporated as a model anticancer drug, and its release profile was evaluated at pH 5.5, 6.8, and 7.4. Release kinetics were analyzed using multiple mathematical models, with Korsmeyer-Peppas model providing the best fit, suggesting anomalous transport governed by diffusion and polymer relaxation mechanisms. Cytocompatibility of MNs formulations was assessed through indirect contact MTT assays using human fibroblast 1132SK cells. Cell viability remained above the threshold established by ISO 10993-5 standard, indicating low cytotoxicity and biocompatibility. Overall, these results demonstrate that poly(DexMA-co-MAA) hydrogel MNs represent a promising platform for controlled drug delivery.