Tofacitinib Citrate-loaded Nanoparticle Gel for the Treatment of Alopecia Areata: Response Surface Design, Formulation and In vitro-in Vivo Characterization.

Objective: The purpose of this research was to optimize the design and construction of nanoparticle gel (TFN-NPs) loaded with tofacitinib citrate (TFN) using poly lactic co glycolic acid (PLGA).

Method: PLGA (A) as the polymer, polyvinyl alcohol (PVA) (B) as the stabilizer and stirring speed (C) as independent variables were used. TFN-NPs were prepared using single emulsion-solvent evaporation. Box Behnken Design (BBD) was used to determine the optimal component ratio of TFN-NPs based on point prediction.

Results: The entrapment efficiency, particle size, and cumulative drug release of the best-composed TFN-NPs were, respectively, 79.82±0.9%, 236.19±5.07 nm, and 82.31±1.23%; the PDI, zeta potential, and drug loading were, respectively, 0.297±0.21, -30.21±0.94mV, and 69.81±0.16%. Gel formulation employing Carbopol as a gelling polymer was then developed using the optimal TFN-NPs mixture. Gel characterization, drug release, permeation studies, irritation, and pharmacokinetic studies were also conducted. Further solid state and morphology were evaluated using FTIR, DSC, XRD, SEM, TEM, and AFM on the developed topical gel formulation (TFN-NPG) and TFN-NPs. The release and permeation investigations indicated that TFN was slowly released (38.42±2.87%) and had significantly enhanced penetration into the epidermal membrane of mice. The cumulative irritation score of 0.33 determined during testing suggested little discomfort. The generated nanogels are stable and have a high drug penetration profile over the skin, as shown by the findings. When compared to both pure TFN solutions, TFN-NPs and TFN-NPG demonstrated superior pharmacokinetic properties.

Conclusion: Based on the results, the NPs and NPG formulations were depicted to enhance the activity of TFN compared to the free drug solution. TFN could be a safe and effective treatment for Alopecia areata. The tofacitinib citrate NPG could be a clinically translatable, safer topical formulation for managing Alopecia areata.