Inclusion into PLGA nanoparticles greatly improves the effectiveness of α-bisabolol to inhibit human Dendritic Cell pro-inflammatory activity

a-bisabolol, a natural sesquiterpene alcohol, has generated considerable interest for its antiinflammatory activity. Since the mechanisms of this anti-inflammatory action remain poorly understood, we investigated whether a-bisabolol affects the release of pro-inflammatory cytokines IL-12, IL-23, IL-6, and TNFa by human dendritic cells (DCs). We found that a-bisabolol did not induce the secretion of these cytokines and did not affect their release induced upon DC challenge with lipopolysaccharide (LPS), a well-known immune cell stimulator. As a-bisabolol is scarcely ingested by the cells, we wondered hether the inclusion of a-bisabolol into nanoparticles could favor its internalization by DCs and consequently its effects on cytokine secretion. We then prepared and characterized poly(lactic-co-glycolic acid) (PLGA) nanoparticles, with a dynamic light scattering peak centered at 154 nm and a half width at half maximum of about 48 nm. These particles were unable to affect per se cytokine secretion by both resting and LPS stimulated DCs and were internalized by human DCs as demonstrated by confocal microscopy analysis. We then loaded PLGA nanoparticles with a-bisabolol and we observed that PLGA-associated a-bisabolol did not stimulate the cytokine release by resting DCs, but decreased IL-12, IL-23, IL-6, and TNFa secretion by LPS-stimulated DCs. Our results indicate that abisabolol inclusion into PLGA anoparticles represents a very promising tool for designing new antiinflammatory, anti-pyretic and, possibly, immunosuppressive therapeutic strategies