Relative uptake of minoxidil into appendages and stratum corneum and permeation through human skin in vitro

Abstract

We examined uptake of the model therapeutic agent, minoxidil, into appendages, stratum corneum (SC), and through human skin, under the influence of different vehicles. Quantitative estimation of therapeutic drug deposition into all three areas has not previously been reported. Finite doses of minoxidil (2%, w/v) in formulations containing varying amounts of ethanol, propylene glycol (PG), and water (60:20:20, 80:20:0, and 0:80:20 by volume, respectively) were used. Minoxidil in SC (by tape stripping), appendages (by cyanoacrylate casting), and receptor fluid was determined by liquid scintillation counting. At early times (30 min, 2 h), ethanol-containing formulations (60:20:20 and 80:20:0) caused significantly greater minoxidil retention in SC and appendages, compared to the formulation lacking ethanol (0:80:20). A significant increase in minoxidil receptor penetration occurred with the PG-rich 0:80:20 formulation after 12 h. We showed that deposition of minoxidil into appendages, SC, and skin penetration into receptor fluid were similar in magnitude. Transport by the appendageal route is likely to be a key determinant of hair growth promotion by minoxidil.

Delivery of drugs applied topically to the skin

“…Vehicles can be important, as their effects on the skin can alter the interaction of the penetrant with the skin. For example, the authors have shown Review that a vehicle such as propylene glycol can alter the properties of the SC, so that the solubility of the active drug minoxidil in the membrane is increased [47]. The importance of membrane solubility was seen in other work with phenols, where it was found that their maximum flux through excised human skin was determined by their solubility in the SC, which was in turn influenced by the vehicle [48].…”

“…It can also be preferentially targeted, as seen in work from this laboratory, where the authors showed preferential follicular delivery of caffeine in vivo [109] at early times, as well as formulationdependent minoxidil penetration in vitro [47]. The Lademann group has pioneered much of the work on follicular drug penetration using nano-or micro-particles as drug carriers [105], advancing the approach that follicles can be used as reservoirs and targets for drug, immune or gene therapy.…”

Solid Lipid Nanoparticles: Technological Developments and in Vivo Techniques to Evaluate Their Interaction with the Skin

“…However a perception of the difficulty of repeated partitioning between lipophilic and hydrophilic compartments in the SC led to this pathway being regarded as unlikely in most cases. There is considerable interest in targeted follicular delivery with tailored drug formulations [Grice et al 2010] or nanoparticle-bound drugs [Lademann et al 2007,Souto &Muller 2008. Hair follicles were regarded as insignificant as potential routes for drug delivery, covering only 0.1% of the human skin surface area, their complex vascularisation and deep invagination with a thinning SC has led to a reappraisal of this view.…”

Targeted skin delivery of topically applied drugs by optimised formulation design

“…Ethanol is a volatile solvent and evaporation can lead to increased drug concentration and a greater driving force for permeation (45,57,165), although this is unlikely to have occurred in our infinite dose experiments here.…”

“…Different ways have been used to investigate the hair follicle as a potential follicular reservoir such as cyanoacrylate skin surface biopsy (15), (45). One aim of follicular targeting is to treat alopecia by growing new follicles bioengineered from the stem cells of patients (46).…”