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Effect of charge and molecular weight on transdermal peptide delivery by iontophoresis

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Published in Pharmaceutical Research. 2005, vol. 22, no. 12, p. 2069-78
Abstract PURPOSE: The study was conducted to investigate the impact of charge and molecular weight (MW) on the iontophoretic delivery of a series of dipeptides. METHODS: Constant current iontophoresis of lysine and 10 variously charged lysine- and tyrosine-containing dipeptides was performed in vitro. RESULTS: Increasing MW was compensated by additional charge; for example, Lys (MW = 147 Da, +1) and H-Lys-Lys-OH (MW = 275 Da, +2) had equivalent steady-state fluxes of 225 +/- 48 and 218 +/- 40 nmol cm(-2) h(-1), respectively. For peptides with similar MW, e.g., H-Tyr-D-Arg-OH (MW = 337 Da, +1) and H-Tyr-D-Arg-NH(2) (MW = 336 Da, +2), the higher valence ion displayed greater flux (150 +/- 26 vs. 237 +/- 35 nmol cm(-2) h(-1)). Hydrolysis of dipeptides with unblocked N-terminal residues, after passage through the stratum corneum, suggested the involvement of aminopeptidases. The iontophoretic flux of zwitterionic dipeptides was less than that of acetaminophen and dependent on pH. CONCLUSIONS: For the series of dipeptides studied, flux is linearly correlated to the charge/MW ratio. Data for zwitterionic peptides indicate that they do not behave as neutral ("charge-less") molecules, but that their iontophoretic transport is dependent on the relative extents of ionization of the constituent ionizable groups, which may also be affected by neighboring amino acids.
Keywords Acetaminophen/administration & dosage/pharmacokineticsAdministration, CutaneousAlgorithmsAmino Acids/metabolismAnimalsBuffersDipeptides/administration & dosage/pharmacokineticsEar, ExternalHydrogen-Ion ConcentrationHydrolysisIontophoresisMolecular WeightOsmosisPeptides/administration & dosage/chemistry/pharmacokineticsSkin AbsorptionSpectrophotometry, UltravioletSwineTyrosine/metabolism
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PMID: 16170597
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ABLA, Nada et al. Effect of charge and molecular weight on transdermal peptide delivery by iontophoresis. In: Pharmaceutical Research, 2005, vol. 22, n° 12, p. 2069-78. https://archive-ouverte.unige.ch/unige:22641

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Deposited on : 2012-08-29

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