Mechanistic insights into high permeation vesicle-mediated synergistic enhancement of transdermal drug permeation.

To design a nanocarrier platform for enhanced transdermal drug permeation. Gel-based high permeation vesicles (HPVs) were developed and their performance in terms of transdermal flux improvement, release and skin irritancy was assessed. The mechanistic insights of permeation enhancement were explored using confocal laser scanning microscopy, ATR-FTIR, DSC and P NMR. HPVs exhibited as vesicles with uniform size (∼150 nm), extended drug-release profile (∼48 h) and improved transdermal flux. HPVs were also nontoxic and nonirritant to skin. Enhanced vesicle deformability, improved vesicle membrane fluidity and synergistic permeation enhancement action of synergistic combination of permeation enhancer components was found to be responsible for HPV-mediated permeation enhancement. Overall, the study established that HPVs demonstrate a promising therapeutic advantage over conventional transdermal drug carriers.