Development of Artocarpin-Loaded Chitosan Particles for Controlled Release and Inflammatory Application

Artocarpin, a flavonoid derived from <i>Artocarpus altilis</i>, has been reported to exhibit anti-inflammatory and geroprotective activities. In this study, artocarpin was isolated from <i>A. altilis</i> heartwood via maceration followed by chromatographic purification, yielding 0.435% of dried extract with a purity of approximately 81%, as confirmed by HPLC. To enhance the physicochemical stability and biological performance of artocarpin, a chitosan-based microparticle delivery system was developed using 0.1% chitosan cross-linked with 0.5% sodium tripolyphosphate (5:1 ratio). The optimized formulation achieved an encapsulation efficiency of 0.5 µg of artocarpin per mg of particles (loading content 0.05% <i>w</i>/<i>w</i>). Physicochemical analysis revealed that the particles possessed a predominantly spherical morphology with sizes ranging from 1 to 4 µm. The hydrodynamic diameter measured by DLS was approximately 3.3 µm, with a PDI of 0.79 ± 0.18 and a zeta potential of 12.8 mV, indicating acceptable dispersity and colloidal stability for a chitosan-based microparticle system. FTIR and XRD analyses verified successful incorporation of artocarpin into the chitosan matrix. In vitro release studies showed a biphasic pattern with an initial burst within 1-12 h followed by sustained release, reaching approximately 60% cumulative release. The anti-inflammatory activity of the formulations was evident through a dose-dependent reduction in nitric oxide production in LPS-stimulated RAW 264.7 macrophages. The artocarpin-loaded particles (CSPs/AE) suppressed NO levels by 34.33 to 73.19%, with statistically significant decreases at <i>p</i> < 0.05. These results highlight the potential of artocarpin-loaded chitosan microparticles as an effective anti-inflammatory delivery system with promising applicability for osteoarthritis management.