Hydration and N-acetyl-l-cysteine alter the microstructure of human nail and bovine hoof: Implications for drug delivery

Abstract

This work aimed to (a) characterize the microstructure and porosity of human nail and bovine hoof by mercury intrusion porosimetry and SEM image analysis, (b) study the effects of hydration and of N-acetyl-l-cysteine treatment on the microstructure of both membranes, and (c) determine whether the microstructural modifications were associated with changes in drug penetration measured by standard diffusion studies. Bovine hoof surface is more porous than nail surface although there were no differences between the mean surface pore sizes. Hydration and N-acetyl-l-cysteine increased the roughness and apparent surface porosity, and the porosity determined by mercury intrusion porosimetry of both membranes. Pore-Cor™ was used to generate tridimensional structures having percolation characteristics comparable to nail and hooves. The modeled structures were horizontally banded having an inner less-porous area which disappeared upon treatment. Treatment increased the predicted permeability of the simulated structures. Triamcinolone permeation increased significantly for hooves treated N-acetyl-l-cysteine, i.e., the membranes for which microstructural and permeability changes were the largest. Thus, microstructural changes determined via mercury intrusion porosimetry and subsequently modeled by Pore-Cor™ were related to drug diffusion. Further refinement of the technique will allow fast screening of penetration enhancers to be used in ungual drug delivery.

Effects of Iontophoresis, Hydration, and Permeation Enhancers on Human Nail Plate: Infrared and Impedance Spectroscopy Assessment

“…The treatment with N-acetyl-L-cysteine further disrupts the structure by breaking disulphide bonds and causes increased swelling (40). On the other hand, both hydration and N-acetyl-L-cysteine alter nail microstructure, increasing its porosity (9). This is consistent with ion transport being facilitated (i.e., increased conductivity) through the swollen, more porous structure as implied by the IS data since the fraction of conductive sites is increasing.…”

“…The effects of N-acetyl-L-cysteine on the amide signals are the most notable of the treatments considered in the current work, in accord with this enhancer's ability to break disulphide bonds and to provoke conformational changes and increased water access to additional sites in the protein (6,7,8). Corroborating this deduction is recent evidence from scanning electron microscopy and mercury intrusion porosimetry (9) that N-acetyl-L-cysteine increases the apparent surface porosity of human nails to a significantly greater extent than simple hydration.…”

“…While topical treatments minimize systemic adverse effects, and avoid the pain associated with intralesional injections, they have limited efficacy (1-4) due primarily to the nature and structure of the nail plate that severely limit drug penetration to the target site of action (5,6). Much research has examined strategies to improve drug delivery to and across the nail (6)(7) including the use of penetration enhancers, such as N-acetyl-L-cysteine which breaks disulphide bonds in keratin, the main constituent of the nail plate (6)(7)(8)(9). Another approach is iontophoresis (10) which involves drug administration to the nail with the application of a small electrical current to enhance molecular transport.…”

“…Elsewhere, some differences in the amide I region of the spectra of nails from diabetic and nondiabetic patients have been noted (19), whereas another FTIR study revealed no changes in the spectral features associated with disulphide bonds in nails post-hydration (9).…”

D-optimal Design and Development of Microemulsion Based Transungual Drug Delivery Formulation of Ciclopirox Olamine for Treatment of Onychomycosis

“…Keratolytic agents, e.g., urea and salicylic acid promote nail softening and swelling via denaturation of keratin fibers [8] . The sulfhydryl compounds, e.g., thioglycolic acid [9,10] , N-acetyl-lcysteine [11,12] , N-(2-mercaptopropionyl) glycine [13] and 2-mercaptoethanol [12] significantly enhance porosity of nail plates.…”