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

Elena Cutrín-Gómez,M Delgado-Charro,José Gómez-Amoza,Soledad Anguiano-Igea,Francisco Otero-Espinar

doi:10.3390/pharmaceutics10040273

Elena Cutrín-Gómez, M Delgado-Charro + Show 3 more

Open Access

https://doi.org/10.3390/pharmaceutics10040273

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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.

Highlights

Ungual drug delivery has been receiving increasing attention in the past few years [1,2]
The chemicals Lactic Acid (LAC), PK, AC, CB and Sodium lauryl sulfate (SLS) significantly modified the structure of the nails and hooves, making them more permeable to drug diffusion
This capability identifies them as penetration enhancers for the nail

Summary

Introduction

Ungual drug delivery has been receiving increasing attention in the past few years [1,2]. The objective pursued with an ungual topical therapy is the attainment of, at least, the minimum therapeutic concentration in every layer of the nail relevant to the pathology considered, including the deepest ones This is a challenging task since the nail layer, besides being much thicker than the stratum corneum, presents completely different physicochemical and structural characteristics [3]. For this reason, dermal topical formulations present very low or even no efficacy in ungual drug delivery since the methods used to improve drug penetration into the skin are ineffective in this area of administration [4,5,6,7]. The nail plate represents a more hydrophilic barrier than the skin [12]

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