Formulation and evaluation of repurposed ketoconazole-loaded transferosomal gel for enhanced trichogenic effects

Abstract

This study was focused to formulate and optimize transferosomes encapsulating ketoconazole (KTZ) for its repurposed use as a hair growth promoting agent. Ketoconazole exerts trichogenic effect in patients with androgenic alopecia androgen by acting on receptors present in keratinocytes and sebocytes of the scalp. This necessitates the penetration of ketoconazole into deep epidermal and dermal layers for exerting trichogenic effect. Transferosomes have been reported to improve drug penetration owing to their deformable vesicular structure. Thus, in the present work, transferosomal gel loaded with ketoconazole was developed with the intention to enhance drug permeation and improved hair proliferation activity. Solvent evaporation method has been adopted for the formulation of transferosomes and then optimized by quality by design approach. KTZ-TF (ketoconazole-transferosomes) were assessed for particle size, entrapment efficiency (%EE), surface charge, and morphology. The optimized KTZ-TF formulation demonstrated particle size of 151.22 ± 1.3 nm, PDI index of 0.191 ± 0.034, and ζ potential of –33.05 ± 01.3 mV, respectively. The developed formulation was further added into gel and compared with commercially available product. It was concluded that KTZ-TF gels showed control drug release (89.1 ± 2.12%) for 9 h. The in vivo skin irritation test demonstrated that the gel formulation caused minimal irritation and was well accepted by the scalp. In vivo qualitative hair growth activity demonstrated improved hair growth with the developed formulation in comparison to marketed KTZ. Histopathological studies also corroborated the findings through demonstrating increase in number of hair follicles. Hence, this study concluded that ketoconazole-loaded transferosomes are efficacious in hair growth activity.