Formulation and evaluation of folic acid-loaded binary ethosomes for enhanced skin permeation

Diabetes-related foot ulcers are a serious health concern and can have detrimental impacts on both physical and mental health. The objective of present study was to prepare folic acid-loaded binary ethosomes. The cold technique was used to prepare the folic acid-loaded binary ethosomes formulation, and evaluated for vesicles size, PDI, zeta potential, FTIR, entrapment efficiency, drug loading. Further the optimized binary ethosomes formulation was converted to gel formulation and assessed for in-vitro drug release, ex-vivo skin penetration, and formulation stability. The optimized binary ethosomes formulation F6 exhibited a vesicles size of 401.8 ± 1.2 nm, with a PDI of 0.32 and a zeta potential of − 29.67 ± 0.5 mV. The entrapment efficiency was found to be 82.24 ± 1.2%. The comparative in vitro drug release profile of the binary ethosomes formulation gel showed a significantly higher release (76.21%) compared to the control gel (39.32%) at 1440 minutes. In ex vivo permeation studies, the flux of the binary ethosomes -loaded gel was 4.98 µg/cm²/h at 2160 minutes. Organoleptic evaluation revealed that the formulated gel was yellowish in color, odorless, and had a pH of 5.5. Rheological studies confirmed that the formulation followed a non-Newtonian shear-thinning behavior, which is favorable for topical application. Overall, optimized F6 was identified as the best formulation based on its physicochemical properties, drug release performance, and rheological characteristics. Hence, the developed folic acid loaded binary ethosomes gel showed potential for improving folic acid efficacy in topical administration.