Dual-Responsive Poly(N-Isopropylacrylamide) Hydrogel Loaded with Poly-l-Lactic Acid Microparticles Encapsulating Boesenbergia Rotunda Extract for Enhanced Topical Delivery

In response to the pH and temperature alterations characteristic of atopic dermatitis (AD), we developed a dual pH- and thermoresponsive hydrogel as a drug delivery system model. The thermoresponsive polymeric-based hydrogel incorporated pH-responsive microparticles encapsulating betamethasone dipropionate (BD) and hexane extract derived from Boesenbergia rotunda. PLLA-V6-OEG3 microparticles were prepared using an emulsification-solvent evaporation method, and their physicochemical properties were subsequently determined. Monodisperse spherical and negatively charged microparticles were obtained in the range of 1–4 μm (polydispersity index, PDI < 0.5) with 98% BD encapsulation efficiency. Notably, the microparticles supplemented with the hexane extract (MP HE BD) exhibited the most rapid release under mildly acidic conditions (pH 6.0). Also, our drug carrier hydrogel was fabricated using poly(N-isopropylacrylamide) (PNIPAM) and N,N′-methylene bis acrylamide (BIS), which were cross-linked using a UV irradiation method. The PNIPAM-BIS hydrogel incorporated with particles demonstrated significant enhancements in both the swelling ratio (>600%) and swelling transition (>250%). The hydrogels were further investigated for ex vivo skin retention and permeation in AD-like mouse skin. The findings revealed that the formulated PNIPAM-BIS3 hydrogel loaded with MP HE BD microparticles facilitated the topical delivery of BD, resulting in a deposition of 31.01 ± 1.78 μg/cm2 on the mice's skin. Remarkably, the addition of B. rotunda hexane extract, which mainly incorporated pinostrobin, was found to contribute to the topical release of BD. The PNIPAM-BIS3 hydrogel loaded with PLLA-V6-OEG3 microparticles supplemented with B. rotunda hexane extract holds promise as a smart dual-responsive drug carrier for managing AD skin conditions.