Co-Drug Strategy for Promoting Skin Targeting and Minimizing the Transdermal Diffusion of Hydroquinone and Tranexamic Acid

The study synthesized two co-drugs, HAC and BAC, by conjugating hydroquinone and tranexamic acid (TXA) to improve skin targeting and reduce transdermal diffusion. These co-drugs were stable in aqueous solutions but rapidly degraded to their parent drugs in esterases and skin homogenates. In vitro tests showed that HAC and BAC increased hydroquinone skin deposition by 7.2- and 2.4-fold, respectively, and enhanced TXA deposition by 3- and 2-fold compared to their individual applications. In vivo experiments further confirmed these enhancements. The co-drugs, especially BAC, demonstrated significantly lower transdermal penetration, indicating better skin targeting. Both co-drugs showed strong affinities for the viable epidermis/dermis and utilized hair follicles as reservoirs for delivery. Daily application for 7 days did not cause skin irritation, making HAC and BAC promising candidates for treating skin hyperpigmentation.