Nom du corpus

Corpus Systématique Animale

Titre du document

Iontophoresis of Bases, Nucleosides, and Nucleotides

Lien vers le document
Éditeur
Springer (journals)
Langue(s) du document
Anglais
Type de document
Research-article
Mots-clés d'auteur
  • iontophoresis
  • electroosmosis
  • transdermal delivery
  • skin penetration
  • bases
  • nucleosides
  • nucleotides
Nom du fichier dans la ressource
Mammiferes_v2b_01393
Auteur(s)
  • Ronald van der Geest 1
  • Frédérique Hueber 1
  • Francis C. Szoka Jr 1
  • Richard H. Guy 1
Affiliation(s)
  • 1) Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California San Francisco, 94143-0446, San Francisco, California
Résumé

Purpose. To investigate whether transdermal iontophoresis may be potentially useful for delivery of oligonucleotide drugs, the electro-transport of representative bases (uracil and adenine), nucleosides (uridine and adenosine) and nucleotides (AMP, ATP, GTP and imido-GTP) across mammalian skin in vitro has been considered. Methods. While the passive permeability of all compounds investigated (from 1 mM solutions at pH 7.4) was very low, the application of constant current iontophoresis (0.55 mA/cm2) significantly enhanced the transport of both charged and uncharged species. Results. The efficiency of delivery depended only weakly upon lipophilicity, varied quite linearly with concentration (for AMP and ATP), was inversely sensitive to molecular weight, and was strongly influenced by charge. Neutral solutes were delivered better from the anode than the cathode, as expected; post-iontophoresis, passive permeabilities were greater than those of the untreated controls, suggesting that iontophoretically-induced changes in barrier function cannot be completely repaired in in vitro model systems. The triphosphate nucleotides, ATP and GTP, were essentially completely metabolized (presumably to their corresponding mono-phosphates) during their iontophoretic delivery, while imido-GTP was apparently resistant to enzymatic attack; however, comparison of the transport data from AMP and ATP suggested that ATP metabolism occurred primarily after the rate-limiting step of iontophoresis. Conclusions. The results obtained are consistent with the general patterns of behavior previously observed in investigations of amino acid and peptide electrotransport. It remains to be seen whether extension of the research described here to larger oligonucleotide species is a feasible long-term objective.

Catégories Science-Metrix
  • 1 - health sciences
  • 2 - clinical medicine
  • 3 - pharmacology & pharmacy
Catégories INIST
  • 1 - sciences appliquees, technologies et medecines
  • 2 - sciences biologiques et medicales
  • 3 - sciences biologiques fondamentales et appliquees. psychologie
Catégories Scopus
  • 1 - Health Sciences ; 2 - Medicine ; 3 - Pharmacology (medical)
  • 1 - Physical Sciences ; 2 - Chemistry ; 3 - Organic Chemistry
  • 1 - Life Sciences ; 2 - Pharmacology, Toxicology and Pharmaceutics ; 3 - Pharmaceutical Science
  • 1 - Life Sciences ; 2 - Pharmacology, Toxicology and Pharmaceutics ; 3 - Pharmacology
  • 1 - Life Sciences ; 2 - Biochemistry, Genetics and Molecular Biology ; 3 - Molecular Medicine
  • 1 - Life Sciences ; 2 - Biochemistry, Genetics and Molecular Biology ; 3 - Biotechnology
Catégories WoS
  • 1 - science ; 2 - pharmacology & pharmacy
  • 1 - science ; 2 - chemistry, multidisciplinary
Identifiant ISTEX
0D5A29F3533F228E91B0B08312F681983EF91E9F
Revue

Pharmaceutical Research

Année de publication
1996
Présence de XML structuré
Non
Version PDF
1.3
Score qualité du texte
4.966
Sous-corpus
  • Mammiferes
Type de publication
Journal
ark:/67375/1BB-JX33MWGH-6
Powered by Lodex 9.3.8