Effect on Nail Structure and Transungual Permeability of the Ethanol and Poloxamer Ratio from Cyclodextrin-Soluble Polypseudorotaxanes Based Nail Lacquer

Abstract

Aqueous-based nail lacquers have shown potential in promoting the diffusion of drugs into the nail. In our laboratory, we have recently developed a transungual delivery system based on an aqueous dispersion of cyclodextrin-poloxamer soluble polypseudorotaxanes, supramolecular host−guest assemblies that improves the drug permeation into the nail. However, the high-water content and the rheological and adhesive properties of this lacquer negatively affect properties that play a fundamental role in the patients’ acceptance such as stickiness, nail film formation or drying rate, properties. In this work, we have optimized the composition of these lacquers to improve these properties whilst maintaining good drug permeation profiles. Incorporating ethanol into the vehicle and reducing the proportion of Poloxamer 407 (PL), provided a good strategy. The use of hydro-ethanolic mixtures (>50% ethanol) and the reduction of the poloxamer concentration significantly improved the lacquer drying speed by reducing the stickiness and promoting film formation on the nail surface. Additionally, in a surprising way, the use of hydro-ethanolic vehicles further enhanced the permeation of ciclopirox olamine and clobetasol propionate, used for the treatment of onychomycosis and nail psoriasis respectively, into the nail and hooves.

Optimization of Drug Permeation from 8% Ciclopirox Cyclodextrin/Poloxamer-Soluble Polypseudorotaxane-Based Nail Lacquers

“…This decrease may be caused by a reduction in the hydration and swelling of the hoof structure, producing a reduction in the hoof matrix porosity. Previous work has shown the importance of the porosity and pore distribution of the nail matrix in the nail permeability of antifungals and corticosteroids [10,[15][16][17]. Therefore, of all the alcohols tested, ethanol was the most suitable for inclusion in lacquer preparations.…”

“…In this sense, Monti et al in 2011 validated the bovine hoof as a model for infected human toenail to study in vitro ciclopirox transungual permeation [22]. Additionally, there are different previous works that demonstrate the usefulness of the bovine hoof model to establish comparisons in the ability to penetrate the nail of drugs from different formulations [11,[15][16][17].…”

“…Some different physical and chemical enhancement techniques have been proposed to improve the efficacy of topical treatments for onychomycosis. These techniques include the abrasion or the ablation of the nail plate [3], the use of laser treatment [3], iontophoresis [8,9], aqueous or water-alcoholic solutions [7,[10][11][12][13][14][15][16], cyclodextrins [15,16], or chemical penetration enhancers [10,17].…”

“…Numerous studies suggest that nail hydration plays a highly significant part in the ability of active ingredients to permeate the nail plate [7,[10][11][12][13][14][15][16][17]. This has meant that organic lacquers are starting to be replaced by water-soluble bases, which moreover allow better drug penetration into the nail.…”

“…To dissolve better still the lipophilic active ingredients, in 2018 Cutrín-Gómez et al [15] studied the effect of including alcohol on drug penetration of the nail using soluble polypseudorotaxane lacquers. The authors were surprised to find that when the water component was replaced with water-ethanol mixtures, instead of reducing penetration, which could be expected since ethanol should reduce hydration, what actually happened was that the rate and degree of penetration of ciclopirox olamine and clobetasol propionate were significantly increased in the bovine hoof model and human nail.…”