Hair follicle targeting with curcumin nanocrystals: Influence of the formulation properties on the penetration efficacy

Abstract

Nanocrystals are a universal formulation approach for improved drug delivery of poorly water-soluble drug substances. Besides oral application, also topical application of the nanocrystals is feasible, because the increased kinetic solubility of the nanocrystals results in an increased concentration gradient, thus fostering passive, dermal penetration. Nanocrystals are also promising for targeting drug substances into the hair follicle. After penetration into the hair follicle, the nanocrystals could form a depot from which the active is released into the hair follicle. Thus, leading to a long-lasting and very efficient dermal drug delivery. The efficacy of nanocrystals to penetrate the hair follicles and the influence of the vehicle in which the nanocrystals are suspended was not yet investigated. Therefore, in this study curcumin nanocrystals with a size of about 300 nm were produced and incorporated into gels with different properties. The efficacy to penetrate the hair follicles, as well as the passive, dermal penetration, was assessed on the ex-vivo pig ear model. Nanocrystals were efficiently taken up by the hair follicles and reached the lower part of the infundibulum. This region is optimal for efficient drug delivery because the barrier of the lower infundibulum is not fully developed and thus more permeable, which results in a less hindered passive diffusion of drug substances. The penetration efficacy of the nanocrystals into the hair follicles was not affected by the different types of vehicles, which represented either oleogels or hydrogels that varied in viscosity as well as in the type and the concentration of the gelling agent. All gels possessed a shear-thinning flow behavior and it is hypothesized that all gels fluidized during the skin massage, whereby leading to similarly low viscosities than the aqueous nanosuspension and thus to similar penetration results. The passive, dermal penetration of curcumin was different for the different gels and the main driving parameter leading to good passive diffusion was caused by good skin hydrating properties of the vehicle. The best passive penetration was achieved from hydrogels that contained a humectant. However, the addition of the humectant reduced the efficacy of the nanocrystals to penetrate the hair follicle. Data so far, therefore, suggest that hair follicle targeting with nanocrystals that are suspended in water or simple, shear-thinning gels is highly effective. However, the addition of other excipients, e.g. humectants, to these vehicles might cause changes in the penetration profiles. More research in this regard is needed to understand these observations in more detail.