Enhanced follicular delivery of minoxidil to human scalp skin using cetosomal formulation.

BACKGROUND: Androgenetic alopecia (AGA) is a common condition marked by progressive hair follicle miniaturization, for which topical minoxidil remains a first-line therapy. However, conventional hydroalcoholic formulations are associated with poor scalp retention, rapid drug loss, and local irritation. This study evaluated the follicular targeting, skin retention, and mechanistic behavior of a cetosomal minoxidil formulation. METHODS: Cetosomal minoxidil (5%) was prepared using patented technology and characterized for size, morphology, and zeta potential. Drug release was assessed by dialysis. Ex vivo penetration and follicular uptake were evaluated in Franz diffusion cells using porcine ear skin, and in vivo penetration was assessed in rats. A randomized, open-label, three-arm clinical pilot study (n = 12) was conducted in males with AGA (Norwood III-V), to compare once-daily cetosomal minoxidil (OCM), twice-daily cetosomal minoxidil (TCM), and twice-daily minoxidil solution (TMS). Scalp penetration was quantified by gamma scintigraphy. RESULTS: Cetosomes were submicron vesicular structures with a bimodal size distribution (∼500 nm) and a zeta potential of -29.5 mV. A biphasic release profile was observed, with an initial burst followed by sustained release. Ex vivo studies demonstrated significantly higher skin retention (up to ∼5.6-fold) and lower transdermal permeation than the conventional solution. Follicular targeting was significantly enhanced. DSC, FTIR, and XRD analyses confirmed lipid disruption, reduced crystallinity, and increased fluidization of the stratum corneum. In vivo imaging showed enhanced skin retention, penetration, and localized distribution of cetosomes. Clinical scintigraphy studies demonstrated significantly greater scalp penetration with cetosomal minoxidil; notably, once-daily cetosomal minoxidil achieved superior penetration compared to twice-daily conventional minoxidil, with no detectable systemic absorption. CONCLUSION: Cetosomal minoxidil enhances topical delivery via lipid fluidization, follicular targeting, and sustained release, offering improved efficacy, reduced systemic exposure, and the potential for less frequent dosing in AGA management.