Skin permeation enhancement of nicotinamide through using fluidization and deformability of positively charged ethosomal vesicles: A new approach for treatment of atopic eczema

Abstract

For the treatment of atopic eczema, the drug penetration of the relevant skin layers is considered to be a major scientific concern. In this study, a new formulation which is based on positively charged ethosomes as drug carriers were prepared and evaluated for their efficacy in penetrating the stratum corneum and accumulating in the skin. The proposed mechanism of skin permeation and retention is based on the dual effect of ethanol as the main component of the ethosomes and stearylamine as a positive charge inducer. A statistical Box- Behnken experimental design was deployed in this study with the use of three variables at three levels; phospholipid concentration, propylene glycol concentration, and ethanol concentration. The prepared formulations were characterized for entrapment efficiency, vesicle size and percent drug released after 6 h. The vesicle size of the prepared formulations was ranging between 18.12 ± 9.19 and 528.1 ± 21.75 nm, while the entrapment efficiency ranged between 86.92 ± 1.34 to 94.15 ± 1.41% and percent drug released after 6 h was ranging between 6.73 ± 0.12 and 99 ± 3.12%. After entering the different responses of the formulations into the statistical software, two formulations were generated as optimized formulations and subjected to the study of the effect of stearylamine as a positive charge inducer on the retention of nicotinamide inside the skin. In vivo testing of the thermosensitive positively charged ethosomal gel of nicotinamide on induced eczema in animal models revealed an enormous recession of inflammatory reaction associated with eczema in addition to the significant reduction of corneocytes maturation.