Multimodal lemongrass oil based topical nanoemulgel ingrained with ferulic acid for wound healing activity

Abstract

The lemongrass oil (LMGO) obtained from Cymbopagan citratus betrays anti-bacterial and anti-oxidant properties. A natural anti-oxidant, ferulic acid (FA) is an angiogenic agent found in vegetables, fruits exhibiting potent anti-inflammatory activity aiding in wound healing process. This investigation was aimed to formulation and optimization of the FA loaded LMGO nanoemulsion (NE) by phase inversion composition method, that has not been well explored by using Box Behnken design (BBD). The surface-active parameters of surfactant mixture (Smix) were evaluated for the selection of Smix ratio in conjunction with conventional pseudo ternary phase diagram. The surface-active parameters included critical micelle concentration (CMC), surface excess concentration (Гmax), minimum surface area adsorbed by surfactant molecules (Amin), effectiveness of adsorption (Πcmc) along with Gibbs thermodynamic parameters for micellization and adsorption. The BBD was employed to optimize the formulation by studying the interaction effects of four independent variables including oil (X1), surfactant mixture (X2), stirring speed (X3), and stirring time (X4) on three responses such as, mean droplet size (Y1), polydispersity index (PDI) (Y2) and percentage transmittance (Y3). At the optimal variable levels (X1 = 10%;X2 = 30%;X3 = 500 rpm and X4 = 5 min), the responses were found to be 26.15 ± 0.58 nm, 0.04 ± 0.01 and 99.76 ± 0.06% for Y1, Y2, Y 3, respectively. The optimized NE exhibited stability in terms of droplet size, PDI, percentage transmittance and surface tension on 5, 10 and 100 times dilution with water. These findings may be useful for designing NE with low energy methods with greater kinetic stability for therapeutic applications. The FA content was determined and found be 98.11 ± 0.51%. The optimized FA loaded NE (FLGO) was incorporated with 2% carbopol®940 for the development of nanoemulgel. The developed FA loaded nanoemulgel (FLGO-G) system demonstrated the pseudoplastic behaviour, desirable for topical application. The blank lemongrass oil nanoemulsion loaded gel (LGO-G) and FLOG-G formulation showed 52.82 ± 0.33% and 75.62 ± 0.16% of DPPH free radical % inhibition. The formulations also showed in-vitro antibacterial activity against S. aureus. The in vivo wound healing efficacy of LGO-G and FLGO-G were studied in male wistar rat, the levels of IL-6 and TNF-α reduced to greater extent.