Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 602, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120607
Keywords
Transdermal drug delivery; Fractional laser ablation; Tape stripping; Protein delivery; Iontophoresis
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The study found that skin barrier impairment affects the iontophoretic transport of both low and high molecular weight permeants, with removal of the stratum corneum not always leading to increased iontophoretic delivery. The decrease of electroosmotic flow and facilitated transport of ions impacted cation delivery by anodal iontophoresis, but the effects were partly offset by enhanced passive diffusion. Decreased electroosmosis favored cathodal electrotransport.
The effect of skin barrier impairment on the iontophoretic transport of low (acetaminophen (ACM), lidocaine (LD), ketorolac (KT)) and high molecular weight permeants, (cytochrome c (Cyt c) and ribonuclease T1 (RNase T1)), was evaluated using tape-stripping (TS) and fractional laser ablation for large-scale and localized barrier disruption. Interestingly, removal of the stratum corneum did not invariably lead to an increase in iontophoretic delivery of the permeants. Decrease of electroosmotic (EO) flow and facilitated transport of Cl- ions in the cathode-to-anode direction, which reduced cation electromigration (EM), both impacted cation delivery by anodal iontophoresis but the effects were partly offset by enhanced passive diffusion. Decrease in EO increased cathodal iontophoresis of KT but not that of RNase T1. Permeability coefficients confirmed the superiority of EM over EO for small molecules, LD > KT > ACM. A combination of fractional laser ablation and iontophoresis was advantageous for both positively and negatively charged small molecules as passive penetration was significantly enhanced. In conclusion, results demonstrated that (i) skin ablation prior to anodal iontophoresis decreased EO and EM but could be advantageous for delivery if the ablative technique enhanced passive penetration thereby compensating reduction of electrotransport and (ii) reduced EO favored cathodal electrotransport.
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