Buccal application of microneedles coated with an optimized hydrogel containing naproxen and dexamethasone

Inflammation and impaired bone regeneration are major challenges in oral and maxillofacial surgery, necessitating the development of effective drug delivery systems. This study aimed to develop a hydrogel-based microneedle (MN) system for the controlled release of anti-inflammatory and osteogenic drugs. A hydrogel loaded with naproxen sodium (NAS) and dexamethasone sodium phosphate (DEX) using poloxamer 407 (NDgel) was prepared using a low-temperature method and optimized via the Box-Behnken design. The optimized hydrogel exhibited a gelation temperature of 30.87 ± 0.64℃, pH 7.92 ± 0.12, and viscosity 87.47 ± 5.66 cP. Physicochemical evaluations, including differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), confirmed that NAS and DEX were incorporated in an amorphous form. The hydrogel was coated onto microneedles (NDgMN) via a dip-coating method and dried. In vitro drug release studies in artificial saliva showed NAS and DEX release rates of 21.7 ± 5.8% and 19.0 ± 1.8%, respectively, after 5 min. The NDgMN exhibited significantly enhanced permeability, with 48.5% and 48.7% permeability for NAS and DEX after 48 h, compared to 31.0% and 28.8% for the hydrogel alone. The IC₅₀ values of the drug solution and drug-containing gel were 123 µg/mL and 203.2 µg/mL, respectively. NDgel demonstrated concentration-dependent inhibition of nitrogen oxide (NO) production at 1-1000 µg/mL, and alkaline phosphatase (ALP) activity assays revealed a 1.2-fold increase at concentrations above 50 µg/mL. These findings suggest that hydrogel-coated MNs have potential as a novel drug delivery system for reducing inflammation and promoting osteocyte differentiation due to their enhanced permeability and bioactivity.