Enabling Anti-inflammatory Activity through Hyaluronan-coated PLGA Nanoparticles Loaded with Carvacrol

Chronic inflammation is characterized by excessive cytokine production and macrophage infiltration, contributing to disease progression. This study aimed to enhance the therapeutic efficacy and local delivery of carvacrol (CVL), a natural PPAR-γ activator with anti-inflammatory properties, through the development of a poly(lactic-co-glycolic) acid (PLGA)-based nanoparticle delivery system with hyaluronic acid (HA)-dependent macrophage targeting.

Poly(lactic-co-glycolic) acid (PLGA)-based nanoparticles encapsulating CVL (CP NPs) were prepared and coated with 1.5% w/v hyaluronic acid (HA) to form CHP NPs for CD44 receptor-mediated targeting of pro-inflammatory macrophages. Physicochemical characterization, encapsulation efficiency, and drug release profile were evaluated. Cellular uptake and cytokine modulation were assessed in lipopolysaccharide-stimulated macrophages.

CP NPs exhibited a size of 155 ± 3 nm and a zeta potential of -57.7 ± 1.3 mV, while HA coating yielded CHP NPs with a size of 225 ± 18 nm and a zeta potential of -25.5 ± 0.3 mV. Encapsulation efficiency and loading capacity reached 91 ± 5% and 26 ± 7%, respectively. HA coating enhanced nanoparticle internalization by 41% compared to uncoated NPs. A sustained release profile was achieved, with 50 ± 13% of CVL released over 21 days. In macrophages, CHP NPs increased anti-inflammatory cytokines IL-1ra (+ 258%), IL-4 (+ 260%), and IL-10 (+ 40%), while reducing pro-inflammatory cytokines IL-1α (-25%), IL-1β (-36%), and TNF-α (-36%) relative to untreated cells.

HA-coated PLGA nanoparticles effectively delivered CVL, enhancing macrophage targeting and promoting an anti-inflammatory response. This platform offers a promising strategy for treating chronic inflammation-related diseases.