Biological investigation of a supersaturated self-nanoemulsifying drug delivery system of Piper cubeba essential oil

Piper cubeba essential oil (PCEO) is used in many ailments but its mechanism of action is not very well reported especially in the case of pain and inflammation. Therefore, in this work, the mechanism of its anti-inflammatory activity alone and as a supersaturated self-nanoemulsifying drug delivery system (S-SNEDDS) was evaluated. S-SNEDDS formulations of PCEO were developed by an aqueous phase titration method. Thermodynamically stable S-SNEDDSs were characterized based on their droplet size, polydispersity index, zeta potential, viscosity, refractive index, % transmittance and surface morphology. Based on the best physicochemical parameters, the S-SNEDDS F1 was selected for biological investigations in rats. The dose of pure PCEO was 400 mg kg−1 body weight while the S-SNEDDS F1 was administered in two different doses i.e. 40 mg kg−1 and 80 mg kg−1 body weight. The results of this work indicated that pretreatment of PCEO and the S-SNEDDS F1 reduced the exudate volume and polymorphonuclear cell number significantly. Moreover, the levels of MPO, NO and proinflammatory cytokines (TNF-α and IL-β) were also reduced by PCEO and the S-SNEDDS F1 and this observation was also supported by histological observation. The results of the S-SNEDDS F1 were superior compared to PCEO alone even at significantly lower doses. These results indicate the potential of a developed S-SNEDDS in enhancing the therapeutic efficacy of PCEO.