pH応答性ナノ粒子を用いた滑膜標的コルヒチン療法

Conventional gout therapies are associated with severe systemic adverse effects, creating a need for sustained and targeted therapy. This research aimed to prepare Colchicine-EL-100-polymeric nanoparticles for pH-dependent release in gout. Molecular docking was performed to provide supportive insight into the COL-NLRP3 interaction. The nanoparticles were prepared and optimized using a Box-Behnken Design, characterized by FTIR, XRD, DSC, and FE-SEM. Incorporated into a characterized Carbopol934 hydrogel, it was evaluated for in vitro release, ex vivo permeation, and ex vivo fluorescence imaging. The nanoparticles were evaluated in an experimental MSU-induced gout model, along with biochemical and histopathological studies. Docking revealed favourable colchicine binding to NLRP3 (docking score of 39.3). Optimized nanoparticles exhibited favourable particle size (152 ± 2.8 nm) and zeta potential (-27.75 ± 0.25 mV), EE% (89.60 ± 0.3%), indicating physicochemical stability. FTIR showed no evidence of chemical incompatibility, XRD indicated amorphization, and DSC supported these findings. In vitro studies showed pH-dependent release (84.3 ± 2.67% at pH 6.8 vs. <20% at pH 7.4 in 24 h), restricted drug release at pH 7.4, with preferential release observed at pH 6.8. Ex vivo fluorescence imaging confirmed penetration (354 μm) within dermal layers with sponge-like restructuring of stratum corneum lipids. In vivo, the formulation reduced inflammation, with IL-6 suppression (92.5 ± 3.62 pg/mL vs. 495.23 ± 32.12 pg/mL). This formulation provides sustained, pH-responsive release and shows therapeutic potential for localized management of gout.