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.

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The interactions between poloxamer 407 (Pluronic F127, PF127) and two hydrophilic derivatives of beta-cyclodextrin, i.e., hydroxypropyl-beta-cyclodextrin (HPbetaCD; molar substitution (MS) 0.65) and methylated-beta-cyclodextrin (MbetaCD; MS 0.57), were characterized by means of surface tension measurements, pi-A isotherms, isoperibol microcalorimetry, 1H NMR, and rheometry. An effective complexation of poloxamer with the two CDs was evidenced as a change in the surface pressure of the pi-A isotherm of PF127 on a subphase of CD solution, with a positive excess being observed at the expanded region and a negative excess at the collapsed region. Such changes indicated that when the CD lies with the main axis perpendicular to the interface at low pressure no complexation occurs, but as the pressure increases and the CDs eventually change their arrangement to be with the main axis parallel to the interface, the amphiphilic copolymer can form polypseudorotaxanes. Addition of CDs to PF127 micellar solutions led to the exothermic rupture of micelles, a shift in the cmc toward higher values, changes in the chemical shifts of H3, H4, and H5 of MbetaCD and of the methyl groups of PF127, and an increase in the gel temperature. The interaction was stronger between poloxamer and MbetaCD, compared to HPbetaCD, with the stoichiometry of the polypseudorotaxanes being preferably ca. 1:20 in both cases. SEM images revealed formation of nanorods of stacked polypseudorotaxanes. Complexation with a high affinity constant between unimers and CDs in bulk solution was also evidenced by competitive displacement of methyl orange. Feasible structural models of the PF127:CD polypseudorotaxanes at both the air-water interface and in the bulk solution are proposed.

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