Progesterone-induced melasma attenuation via tranexamic acid-loaded nano-liposomes: an alternative dermal therapeutic...

Melasma, a chronic and recurrent hypermelanosis affecting sun-exposed areas, presents a significant therapeutic challenge due to its high relapse rate. Conventional treatments primarily rely on topical depigmenting agents and strict photoprotection. While Kligman's formula remains a cornerstone therapy for epidermal melasma, Tranexamic acid (TA) has gained increasing interest. Topical TA is preferred over oral administration because of its localized action and reduced systemic side effects; however, its efficacy is limited by its hydrophilicity, which results in poor skin permeation and deposition. This study aimed to address these limitations by developing TA-loaded nano-liposomes (TA-Lipo) to enhance drug delivery and improve symptoms of induced melasma. Six formulations (TA-Lipo1 to TA-Lipo6) were evaluated for their in vitro release profile, morphological characteristics, skin permeation, and anti-hyperpigmentation efficacy using a rat melasma model. The prepared TA-Lipo exhibited controlled 24-hour release and favorable characteristics (size: 90-156 nm; zeta potential (ZP): -32 to -41 mV; encapsulation efficiency (EE): 55-78%). The highest-performing formulation (TA-Lipo2) consisted of Phospholipon 90G (PL90G) and Cholesterol (CHO) in a 2:1 ratio with TA at 2 mg/mL. Ex vivo Franz diffusion studies demonstrated a 2.3-fold increase in TA permeation, while Confocal Laser Scanning Microscopy (CLSM) confirmed deep skin infiltration, reaching 122 µm-a 1.74-fold improvement compared with the control solution. Incorporating TA-Lipo2 into a 1% Carbopol 940 bio-adhesive gel (TA-LipoG) provided sustained delivery. This enhanced targeting translated into superior in vivo efficacy in a rat melasma model, where TA-LipoG achieved a 92.5% reduction in MASI score, significantly outperforming Kligman's formula (69.8%). Histological analysis confirmed near-complete resolution of pigmentation and revealed a markedly thicker subcutaneous fat layer (108.9 µm) in the TA-LipoG group compared with the Kligman group (38.5 µm), indicating superior local biocompatibility. Overall, these findings support the use of nano-liposomes within Carbopol gel matrices as a superior, sustained, and localized delivery system for TA in hyperpigmentation treatment.