Formulation Development and Optimization of Glycolic Acid-Loaded Ethanol-Based Niosomes for Enhanced Dermal Delivery and Stability

Glycolic acid (GA), a widely used alpha-hydroxy acid in cosmetic formulations, promotes exfoliation and stimulates fibroblasts in the dermis to synthesize collagen. However, its hydrophilic nature limits penetration through the stratum corneum, reducing its overall efficacy. This study aimed to develop and optimize an ethanol-based niosomal system to enhance GA skin delivery and formulation stability for cosmetic applications. Brij 97 combined with cholesterol at a 1:1 ratio and 10% ethanol produced the optimal formulation. Blank vesicles exhibited a mean vesicle size of 170.53 ± 5.05 nm and a zeta potential of −37.77 ± 2.21 mV, indicating favorable colloidal stability. Incorporation of 10% GA resulted in vesicles with a mean size of 176.93 ± 1.51 nm, a polydispersity index of 0.12 ± 0.02, and an entrapment efficiency of 75.48 ± 0.21%. In vitro permeation studies using Strat-M® membranes demonstrated significantly higher cumulative skin penetration (49.56 ± 8.95 mg/cm2) and sustained release over 24 h compared with a conventional GA solution. Stability testing under heating–cooling cycles and storage at 4 °C showed slight increases in vesicle size while maintaining homogeneity (polydispersity index (PDI) < 0.3). These findings highlight ethanol-based niosomes as an effective strategy for enhancing GA cosmetic performance.