Nanostructured Lipid Carrier-Based Dermal Delivery of Tranexamic Acid for Melasma Management: Current Advances and Future Perspectives

Melasma is a chronic, recurrent hyperpigmentation disorder driven by ultraviolet radiation, hormonal influences, inflammation, vascular changes, and altered keratinocyte–melanocyte signaling. Tranexamic acid (TXA) is an off-label therapeutic option that suppresses melanogenesis primarily through inhibition of the plasminogen–plasmin pathway. Although oral TXA can reduce melasma severity, systemic safety concerns and relapse after discontinuation limit its use. Conventional topical TXA is safer but suffers from poor stratum-corneum penetration, limited epidermal deposition, low local bioavailability, and short cutaneous residence time. Nanostructured lipid carriers (NLCs) offer a promising approach to overcome these limitations through improved drug loading, controlled release, enhanced skin interaction, and prolonged local retention. However, the high aqueous solubility and zwitterionic nature of TXA complicate its incorporation into lipid matrices, making strategies such as hydrophobic ion pairing and double-emulsion systems particularly relevant. This review critically examines the preclinical development of TXA-loaded NLCs for melasma, including disease pathophysiology, TXA mechanisms, limitations of conventional delivery, NLC formulation and preparation, physicochemical characterization, in vitro diffusion, skin tolerability, stability, and translational challenges. Particular attention is given to encapsulation efficiency, skin-deposition evidence, scale-up, sterilization, regulatory considerations, and clinical validation. Current evidence supports TXA-loaded NLCs as a mechanistically rational and preclinically promising dermal delivery platform, but robust skin-deposition studies, long-term stability data, scalable manufacturing, and well-designed clinical trials are still required.