Abstract
This study was intended to develop and optimize agomelatine loaded lipid-based transdermal vesicles (AGLTVs) for the treatment of depression. For the optimization purpose, central composite design was used and the selected independent variables were phospholipid and ethanol. The individual and joined impacts of independent variables were assessed on vesicle size, PDI, and encapsulation efficiency. Further, the optimized agomelatine loaded lipid transethosomes vesicle (AGLTVopt) was evaluated for drug release, skin penetration potential, physicochemical properties and preclinical antidepressant effect on Swiss albino mice. AGLTVopt showed low vesicle size (156.8 nm), high entrapment efficiency (78.57%) and enhanced transdermal flux (18.75 μg/cm2/h). Finally, AGLTVopt was converted to a Carbopol-934 based gel for the ease of transdermal application. The confocal laser scanning microscopy study results also showed enhanced permeation of Rhodamine-B containing AGLTVopt-gel to the deeper layer of skin. The drug release study showed prolonged release of agomelatine and the drug release kinetics followed the Higuchi model. The in-vivo antidepressant activity presented greater improvement in the behavior of AGLTVopt-gel treated group. The histopathology of skin revealed no sign of irritation. This study concluded that the AGLTVopt-gel can be a safe formulation for the brain delivery of agomelatine via transdermal route.
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