title: Effect of charge and molecular weight on transdermal peptide delivery by iontophoresis.
abstract: OBJECTIVE
  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.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, 30 Quai Ernest-Ansermet, 1211, Geneva 4, Switzerland.
authors.forename: Nada
authors.initials: N
authors.lastname: Abla
authors.forename: Aarti
authors.initials: A
authors.lastname: Naik
authors.forename: Richard H
authors.initials: RH
authors.lastname: Guy
authors.forename: Yogeshvar N
authors.initials: YN
authors.lastname: Kalia
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D000465:Algorithms; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002021:Buffers; D004151:Dipeptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D004431:Ear, External; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D007478:Iontophoresis; D008970:Molecular Weight; D009995:Osmosis; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D012869:Skin Absorption; D013056:Spectrophotometry, Ultraviolet; D013552:Swine; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000596:Amino Acids; D002021:Buffers; D004151:Dipeptides; D010455:Peptides; D000082:Acetaminophen; D014443:Tyrosine