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

The study was conducted to investigate the impact of charge and molecular weight (MW) on the iontophoretic delivery of a series of dipeptides. Constant current iontophoresis of lysine and 10 variously charged lysine- and tyrosine-containing dipeptides was performed in vitro. Increasing MW was compen...

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Bibliographic Details
Published in:Pharmaceutical research 2005-12, Vol.22 (12), p.2069-2078
Main Authors: Abla, Nada, Naik, Aarti, Guy, Richard H, Kalia, Yogeshvar N
Format: Article
Language:English
Subjects:
Acetaminophen - administration & dosage
Acetaminophen - pharmacokinetics
Administration, Cutaneous
Algorithms
Amino Acids - metabolism
Animals
Buffers
Dipeptides - administration & dosage
Dipeptides - pharmacokinetics
Ear, External
Hydrogen-Ion Concentration
Hydrolysis
In Vitro Techniques
Iontophoresis
Molecular Weight
Osmosis
Peptides - administration & dosage
Peptides - chemistry
Peptides - pharmacokinetics
Skin Absorption
Spectrophotometry, Ultraviolet
Swine
Tyrosine - metabolism
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Summary:The study was conducted to investigate the impact of charge and molecular weight (MW) on the iontophoretic delivery of a series of dipeptides. Constant current iontophoresis of lysine and 10 variously charged lysine- and tyrosine-containing dipeptides was performed in vitro. 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. 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.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-005-8110-2