A novel approach for dermal controlled release of salicylic acid for improved anti-inflammatory action: Combination of hydrophilic-lipophilic balance and response surface methodology

The present investigation was aimed to develop SA loaded nanoemulsion by implementing response surface methodology (RSM) and hydrophilic-lipophilic balance (HLB) approach, in amalgamation. The concentration of oil phase (Lemongrass oil containing SA, corresponding to HLB from 13.43 to 14.88) and the ratio of surfactants were taken as independent factors while particle size and polydispersibility index as dependent variables in RSM. The droplet size and polydispersibility index of the optimized nanoemulsion (SANE 14) were 134.70 ± 4.51 nm and 0.168 ± 0.011 respectively, corresponding to the HLB value of 14.8. The retention of SA from SANE 14 in skin layers was found to be 97.23% after 24 h study period. Moreover, a 2.8 and 4.13 folds amount of SA from SANE 14 was retained in epidermis and dermis, respectively, when compared with the drug solution. Therefore, the SANE 14 was capable of delivering the SA into the deeper skin layers with notable retention which was further verified by the confocal microscopy images. The TPA induced skin inflammation in mice ear was significantly reduced (80.25%) in terms of ear thickness. Significant inhibition of pro-inflammatory cytokines proved the efficacy of SANE 14. Conclusively, the controlled dermal release of salicylic acid for improved anti-inflammatory action was successfully achieved.