Gallic Acid-Loaded Transethosomal Gel for Enhanced Topical Delivery and Sustained Therapeutic Efficacy in Psoriasis Management: Formulation, Optimization, In Vitro and Ex Vivo Assessment.

Psoriasis is a chronic, non-communicable inflammatory skin disorder for which current treatments are largely limited to symptomatic management. These approaches were often challenged with limitations like inadequate skin penetration, frequent dosing requirements, potential toxicity, and low patient adherence, ultimately compromising therapeutic outcomes and affecting patients' health. To obviate the flaws that are hindering the clinical success, nanotechnology has transpired as a revolutionary treatment alternative. Here, we have fabricated a gallic acid encased transethosomal-loaded gel (GA-TE-loaded gel) for the therapeutic management of psoriasis. The optimized gallic acid encased transethosome (GA-TE) displayed an average particle size of 288.9 ± 12.4 nm, a polydispersity index (PDI) of 0.30 ± 0.04, a zeta potential of -38.3 ± 3.2 mV, and an entrapment efficiency (%EE) of 72.55 ± 4.8% (mean ± SD, n = 3). In vitro release studies revealed a biphasic profile for the GA‑TE-loaded gel, an initial burst followed by a sustained phase, achieving 77.3% release of gallic acid over 24 h., compared to the conventional GA-loaded gel (96.36% release at 4 h.). Furthermore, ex-vivo permeation studies and confocal laser scanning microscopy (CLSM) confirmed superior skin permeability by the GA-TE-loaded gel. The dermatokinetic study further validated that encapsulation of GA within the transethosomal vesicle significantly augments the transportation of therapeutic agent within the epidermal and dermal layers in contrast to conventional drug loaded gel. The nanoformulation exhibited a good safety profile and negligible irritative potential, as evidenced by the low irritation score (IrS) value obtained during the HET-CAM irritation assay. These outcomes suggest that the GA-TE-loaded gel offers significant potential as a future treatment alternative for addressing psoriasis.