Improving the oral bioavailability and anti-inflammatory potential of clove oil-derived β-caryophyllene with a self-nanoemulsifying drug delivery system.

OBJECTIVES

β-Caryophyllene (β-Cary) is known for its anti-inflammatory properties and offers a promising avenue for drug development. This study prepared a lipid-based self-emulsifying system containing clove oil-derived β-Cary and investigated its bioavailability and anti-inflammatory effects upon oral administration in rats.

METHODS

The formulation (β-SNEDDS), composed of β-Cary, surfactant, and lipophilic phase, was evaluated as size, morphology, and rheology.

KEY FINDINGS: β-SNEDDS exhibited Newtonian flow and formed spherical droplets (≈100 nm) in water and phosphate-buffered saline (pH 6.8), with a diameter ~15% higher in PBS, likely due to ionic strength affecting surfactant hydration and interfacial structure. Transmission electron microscopy confirmed spherical particles in simulated gastrointestinal medium. β-SNEDDS showed twice the oral bioavailability of β-Cary. This phenomenon allowed β-SNEDDS to reduce carrageenan-induced paw edema and pleural polymorphonuclear leukocyte recruitment in the pleural cavity of rats, showing greater efficacy than β-Cary. Furthermore, β-Cary reduced N-Formyl-Met-Leu-Phe (fMLP)-induced leukocyte chemotaxis in vitro, and oral β-SNEDDS or β-Cary reduced rolling and adherent leukocytes in situ in rat microvascular endothelium. Notably, β-SNEDDS exhibited a more pronounced effect on rolling behavior.

CONCLUSIONS

β-Cary showed significant anti-inflammatory activity by inhibiting leukocyte migration to the inflamed site. Its β-SNEDDS formulation improved oral bioavailability and additional anti-inflammatory parameters in vivo, beyond those achieved by β-Cary, supporting this approach as a promising oral strategy.