Localized follicular delivery of a JAK inhibitor using optimized PhosGlyNanoVes: a novel approach for alopecia areata treatment.

Localized functional therapy with fewer side effects for alopecia areata (AA) is the major leading problem in the current scenario. A Janus kinase inhibitor, Tofacitinib citrate (TFC), can be explored for treating AA directly at the site of action to avoid systemic toxicity. The current study was designed to formulate and optimize the TFC phospholipon nanovesicles enriched with glycerol (PhosGlyNanoVes) and incorporate it into a gel (GlyNanoGel) with a view to improving its topical delivery in the treatment of AA. PhosGlyNanoVes were prepared using the thin lipid film hydration technique, with different concentrations (20-30% v/v) of Phospholipon 90G (PL90G), Cholesterol, and Glycerol (Gly) as a lipophilic phase, and TFC as a lipophilic drug. The optimization of PhosGlyNanoVes was done using a central composite design with PL90G concentration, Gly concentration, and homogenization time as independent variables, while % entrapment efficiency (%EE), particle size, and cumulative drug release after 12 h were taken as responses. Optimized formulations were loaded into Carbopol 934 gel and characterized for particle size distribution, zeta potential, %EE, vesicle morphology, in vitro and ex vivo drug release, and other characterization techniques, i.e., FTIR, DSC, and XRD, were also conducted for the analysis of drug-excipient compatibility, crystallinity, and vesicle stability. Optimization of PhosGlyNanoVes with 133.34 mg of PL90G, 27.34% Gly, and a 9.5-min homogenization period resulted in a formulation with 89.28% %EE, a particle size of 182.84 nm, and 93.82% TFC release after 12 h with a prediction error of less than 1%. The particle size distribution was found to be less than 0.3, and the zeta potential was observed as - 48.2 mV, confirming the excellent stability of the formulation. A significant decrease in XRD peak intensities from 89.7 to 10.2% indicated a change in the crystalline nature of the drug from crystalline to amorphous within the vesicles. Higher permeation and stability of PhosGlyNanoVes were observed. The optimized PhosGlyNanoVes were shown to possess stability in the nanometer range with a high %EE and release profile, thus demonstrating their promise as a topical delivery system in the treatment of AA with minimal side effects.