Formulation and In Vitro Evaluation of Ashwagandha Extract-Loaded Ethosomal Gel for Diabetes Management

Objective: The aim of the present study to develop, optimize and characterize ethosomal gel formulation loaded with ashwagandha leaf extract for improved transdermal delivery of Withanolide A for enhanced antidiabetic activity Methods: Ethosomes loaded with Ashwagandha leaf extract were formulated by thin film hydration method and optimized by Box-Behnken design. Ethosomes were evaluated for vesicle size, PDI, Zeta potential and entrapment efficiency. Optimized ethosomes were incorporated into carbopol gel base of different concentration and evaluated for various properties such as appearance, homogeneity, pH, viscosity, and spreadability including Ex-vivo skin permeation study. The antidiabetic activity of optimized gel formulation was assessed in vitro using the α-amylase enzyme inhibition assay and compared with the gel formulation loaded with extract. Results: The optimized ethosomes had vesicle size of 59.338± 0.016 nm with polydispersiblity index of 0.412±0.002 and percentage entrapment efficiency of 92.355± 0.024. The ethosomal gel formulation (F3) containing carbopol of concentration 1.5% was chosen as optimized ethosomal gel formulation based on good appearance, required spreadability and viscosity. In addition, it also showed high permeation and sustained release of withanolide A with flux value of 248.5 (µg/cm²/hr) from ethosomal gel formulation in comparison to gel formulation loaded with ashwagandha leaf extract. Ethosomal gel formulation also showed higher percentage of alpha amylase inhibitory activity of 33.66% in comparison to extract loaded into gel base indicating improved antidiabetic activity in vitro. Conclusion: Incorporation ashwagandha leaf extract into ethosomal gel formulation showed enhancement in the solubility and bioavailability of withanolide A for antidiabetic activity and there by proving that ethosomes are potential as nanocarriers in delivering withanolides for the treatment of Diabetes