Indole-2-carboxylic Acid Nanoemulsions: A Novel Approach for Topical Cosmeceuticals with Antioxidant Properties in Human Skin Models.

Bioactive molecules, such as indole alkaloids, have received special attention due to their remarkable pharmacological versatility, particularly their antioxidant activities. Therefore, our objective was to build an engineered delivery system (a topical nanoemulsion), incorporating indole-2-carboxylic acid, and evaluate its antioxidant potential using an ex vivo human skin model. The nanoemulsion was characterized by particle size, polydispersity index, zeta potential, encapsulation efficiency, in vitro release kinetics, and skin permeation profiles. Antioxidant enzyme activities (superoxide dismutase , catalase, glutathione S-transferase) and oxidative stress markers (carbonyl proteins, malondialdehyde) were quantified. Histological and immunohistochemical analyses assessed skin tissue responses, focusing on the oxidative stress markers [8-hydroxy-2'-deoxyguanosine (8OHdG), and 4-hydroxynonenal (4HNE)] and structural tissue markers (type III collagen, and filaggrin). Our results showed that skin permeation studies using human skin explants demonstrated effective barrier traversal, with substantial retention in the stratum corneum and recovery in the receptor compartment, supporting the formulation's potential for transdermal delivery. The nanoemulsion exhibited no cytotoxicity in RAW 264.7 macrophages and attenuated oxidative stress, as evidenced by reduced 4HNE labeling, while enhancing key structural skin markers, including filaggrin, and preserving dermal vascularization, indicating a robust skin recovery response. In conclusion, we observed that the indole-2-carboxylic acid nanoemulsion effectively modulated oxidative stress pathways while simultaneously preserving skin barrier homeostasis. These dual therapeutic actions underscore its potential as a cosmeceutical platform for the management of skin diseases.