Effect of Penetration Enhancers on Drug Nail Permeability from Cyclodextrin/Poloxamer-Soluble Polypseudorotaxane-Based Nail Lacquers

Abstract

Nail delivery has interest for local treatment of nail diseases. Nevertheless, the low permeability of drugs in the nail plaque precludes the efficacy of local treatments. The use of penetration enhancers can increase drug permeability and improve the efficacy of the treatment of nail pathologies. In this work, different chemical substances have been evaluated as potential penetration enhancers. With this aim, the effect of different substances such as sodium lauryl sulfate (SLS), polyethylene glycol 300 (PEG 300), carbocysteine, N-acetylcysteine, lactic acid, potassium phosphate, Labrasol® and Labrafil® in the microstructure, nail surface and drug permeability has been evaluated. The models obtained by mercury intrusion porosimetry and PoreXpert™ software show a more porous structure in nails treated with different enhancers. Permeation studies with bovine hooves and nails revealed that all the hydroalcoholic lacquers developed, and particularly those prepared with SLS, provide better nail penetration of the drugs ciclopirox olamine and clobetasol propionate. Results have shown that the increase of the drug penetration in the nail is caused by the formation of a porous random microstructure and by the decrease of the contact angle between lacquers and the surface or the nail plaque. The presence of SLS produces an improvement in the spreading of the solution on the nail surface and promotes the penetration of the solution into the nail pores. The hydroalcoholic lacquer, elaborated with cyclodextrin/poloxamer soluble polypseudorotaxane and sodium lauryl sulfate as an enhancer, allowed the rate of diffusion and penetration of the active ingredient within the nail to be significantly higher than obtained with the reference lacquers when using either ciclopirox olamine or clobetasol propionate as the active ingredient.

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.…”

Transungual Delivery, Anti-Inflammatory Activity, and In Vivo Assessment of a Cyclodextrin Polypseudorotaxanes Nail Lacquer

“…Softening compounds (urea and salicylic acid) have keratolytic properties and increase water uptake and swell keratin, making it less dense and compact and increasing the pore size [4]. Surfactants such as sodium lauryl sulfate could also alter the protein packing by electrostatic repulsion, induce micelle formation and absorption promotion, and reduce the contact angle between the formulation and nail surface to ensure better water access, increasing swelling [18]. Cyclodextrins are cyclic oligosaccharides and had the ability to form complexes with various active ingredients, involving the active ingredient in the lipophilic center.…”