Design, preparation, and evaluation of liposomal gel formulations for treatment of acne: in vitro and in vivo studies

The study highlights the significance of co-application of bioactive components into liposomal gel formulations and their comparison to azithromycin for treatment of Acne. A Design of Experiments (DoE) approach was utilized to obtain optimized liposomal formulation encapsulating curcumin, with size and zeta potential of similar to 100 nm and similar to 14 mV, respectively, characterized by DLS, HR-TEM, FESEM, and AFM. The curcumin liposomal dispersion depicted excellent stability over the period of 60 days, which was further converted in gel form using Carbopol. Pharmacokinetics of curcumin-loaded liposomal gel showed that T-max for curcumin was achieved within 1 h of post application in both stratum corneum and skin, indicating quick penetration of nano-sized liposomes. Stratum corneum depicted C-max of 688.3 ng/mL and AUC(0-t) of 5857.5 h x ng/mL, while the skin samples displayed C-max of 203.3 ng/gm and AUC(0-t) of 2938.1 h x ng/gm. Lauric acid and azithromycin liposomal gel formulations were prepared as per the optimum parameters obtained by DoE. In antibacterial activity using agar diffusion assay, lauric acid gel formulation revealed similar to 1.5 fold improved antibacterial effect than curcumin gel formulation. Interestingly, their co-application (1:1) exhibited significantly enhanced antibacterial effect against both macrolide-sensitive (1.81 versus 1.25 folds) and resistant strains of P. acnes (2.93 versus 1.22 folds) than their individual counterparts. The in vivo studies in rat ear model displayed a similar to 2 fold reduction in comedones count and cytokines (TNF-alpha and IL-1 beta) on co-application with curcumin and lauric acid liposomal gel compared to placebo treated group.