Abstract
Drug combination therapy is commonly used to treat hyperpigmentation. However, treatment success is often limited due to the insufficient activity of combined drugs. To improve the therapeutic efficacy of drug combination treatment, we synthesized and investigated several conjugates comprising homo- and heterogeneous anti-pigmenting drugs bound to a hyaluronic acid (HA) carrier through distinct biodegradable linkers. These HA-drug conjugates demonstrated a measurable drug release profile in hydrolytic media. Most of the tested conjugates, administered by mesotherapy after UV-light-induced pigmentation in a swine model, presented superior depigmentation over corresponding controls. Among them, the dendron-like conjugate, NH2-TXA-Tris-TXA-(EtCMB)3, that contains only tranexamic acid (TXA), was most effective at depigmenting the swine skin compared to its equimolar mixture of HA and TXA (control). These results emphasize the importance of conjugation depigmenting agents to HA for augmenting the efficacy of treatment and motivate the use of HA as a delivery platform for treatment of various skin disorders.
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