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

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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-NH2 (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.

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Acknowledgment

R.H.G. thanks the U.S. National Institutes of Health (EB-001420) for financial support.

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Author notes

  1. Richard H. Guy

    Present address: Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK

Authors and Affiliations

  1. School of Pharmaceutical Sciences, University of Geneva, 30 Quai Ernest-Ansermet, 1211, Geneva 4, Switzerland

    Nada Abla, Aarti Naik, Richard H. Guy & Yogeshvar N. Kalia

  2. Centre Interuniversitaire de Recherche et d'Enseignement, Pharmapeptides, Site d'Archamps, 74160, Archamps, France

    Nada Abla, Aarti Naik & Yogeshvar N. Kalia

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  1. Nada Abla
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  2. Aarti Naik
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Correspondence to Yogeshvar N. Kalia.

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Abla, N., Naik, A., Guy, R.H. et al. Effect of Charge and Molecular Weight on Transdermal Peptide Delivery by Iontophoresis. Pharm Res 22, 2069–2078 (2005). https://doi.org/10.1007/s11095-005-8110-2

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  • DOI: https://doi.org/10.1007/s11095-005-8110-2

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