Tranexamic Acid-Based Polymeric Micellar Hydrogel for Enhanced Dermal Delivery and Melanin Reduction

Oral and intralesional tranexamic acid (TXA), used in melasma treatment, pose systemic and invasive risks, while topical TXA suffers from poor permeability (logP = -1.6) and retention. The current study aimed to develop a topically effective polymeric micelles (PMs) based product incorporating 5% w/v TXA for deeper skin permeation and efficient melanocyte targeting. Developed PMs were novel in terms of: (i) composition, (ii) high drug loading of 250% with respect to the polymeric matrix, and (iii) transparent system. TXA-PMs had a particle size of 47.0 ± 3.6 nm, exhibited an entrapment efficiency of 81 ± 1.4%, and were transformed into a hydrogel (Hgel) for better skin retention by incorporating 0.5% Carbopol 934P. TXA-PMs Hgel had a pH of 5.7 and demonstrated favorable Newtonian pseudoplastic behavior, diffusion-controlled Higuchi release (>97%) up to 48 h, enhanced skin permeation (93% versus 74% observed with the marketed product), and retention (160% versus marketed product). On the other hand, free TXA in the Hgel matrix and the marketed product were released within 8 h. Three tier safety of TXA-PMs Hgel was demonstrated in <i>in vitro</i> cytotoxicity, <i>in vivo</i> acute toxicity, and biocompatibility tests. It substantially reduced melanin concentration (>50% inhibition) in B16F10 melanoma cell lines in comparison to free TXA Hgel (34%). The accelerated stability studies (6 months) revealed no significant change in the prepared formulations. TXA-PMs Hgel thus offers a promising therapeutic approach for melasma treatment as indicated by its enhanced permeation, stay in skin, and significant reduction in melanin content. Further, the production method is simple, industry amenable, and scalable.