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Effect of Charge and Molecular Weight on Transdermal Peptide Delivery by Iontophoresis

Abla, Nada ; Naik, Aarti ; Guy, Richard ; Kalia, Yogeshvar

In: Pharmaceutical Research, 2005, vol. 22, no. 12, p. 2069-2078

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    Title
    • Effect of Charge and Molecular Weight on Transdermal Peptide Delivery by Iontophoresis
    Author
    • Abla, Nada. School of Pharmaceutical Sciences, University of Geneva, 30 Quai Ernest-Ansermet, 1211, Geneva 4, Switzerland
    • Naik, Aarti. School of Pharmaceutical Sciences, University of Geneva, 30 Quai Ernest-Ansermet, 1211, Geneva 4, Switzerland
    • Guy, Richard. School of Pharmaceutical Sciences, University of Geneva, 30 Quai Ernest-Ansermet, 1211, Geneva 4, Switzerland
    • Kalia, Yogeshvar. School of Pharmaceutical Sciences, University of Geneva, 30 Quai Ernest-Ansermet, 1211, Geneva 4, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Pharmaceutical Research, 2005, vol. 22, no. 12, p. 2069-2078. Springer-Verlag; http://www.springer-ny.com
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:314929
    Summary
    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 = 147Da, +1) and H-Lys-Lys-OH (MW = 275Da, +2) had equivalent steady-state fluxes of 225 ± 48 and 218 ± 40nmol cm−2 h−1, respectively. For peptides with similar MW, e.g., H-Tyr-d-Arg-OH (MW = 337Da, +1) and H-Tyr-d-Arg-NH2 (MW = 336Da, +2), the higher valence ion displayed greater flux (150 ± 26 vs. 237 ± 35nmol 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