TY - JOUR
T1 - Transdermal iontophoresis of amino acids and peptides in vitro
AU - Green, Philip G.
AU - Hinz, Robert S.
AU - Kim, Aeri
AU - Cullander, Christopher
AU - Yamane, Grace
AU - Szoka, Francis C.
AU - Guy, Richard H.
N1 - Funding Information:
This researchw as supported by the U.S. National Institutes of Health (HD-27839), and by grants from Cygnus Therapeutic Systems,S yn-tex Researcha nd Hoffmann-LaRoche. The work summarized here, and presenteda t the Leiden Symposium, has been peer-reviewed and pub- lished as two full papersi n PharmaceuticalR e-search (P.G. Green et al., Pharm. Res. 8 ( 1991 ) 1113-l 120; and P.G. Green et al., Pharm. Res. 8 (1991) 1121-1127).
PY - 1992/7/31
Y1 - 1992/7/31
N2 - The effects of penetrant properties (lipophilicity and charge) and of vehicle pH on the iontophoretically enhanced delivery of amino acids, their N-acetylated derivatives, and eight tripeptides, of the general structure alanine-X-alanine, have been examined in vitro. The penetrants were (a) 9 amino acids (five were zwitterionic, two positively charged and two negatively charged), (b) four N-acetylated amino acids, which carry a net negative charge at pH 7.4, and (c) peptides which were blocked both at the carboxyl terminus using the mixed anhydride reaction with t-butylamine, and at the amino terminus by acetylation with 14C-acetic anhydride; the central residue (X) was varied widely by selecting one of five neutral amino acids, two negatively chargeable moieties (aspartic and glutamic acids), and a positively chargeable species (histidine). Iontophoresis at constant current (0.36 mA/cm2), using Ag/AgCl electrodes, was conducted across freshly excised hairless mouse skin. The diffusion cells used were designed so that both anode and cathode were situated on the same (epidermal) side of a single piece of skin. Overall, it was found that the results of this research support the principle of enhanced peptide delivery across the skin by iontophoresis.
AB - The effects of penetrant properties (lipophilicity and charge) and of vehicle pH on the iontophoretically enhanced delivery of amino acids, their N-acetylated derivatives, and eight tripeptides, of the general structure alanine-X-alanine, have been examined in vitro. The penetrants were (a) 9 amino acids (five were zwitterionic, two positively charged and two negatively charged), (b) four N-acetylated amino acids, which carry a net negative charge at pH 7.4, and (c) peptides which were blocked both at the carboxyl terminus using the mixed anhydride reaction with t-butylamine, and at the amino terminus by acetylation with 14C-acetic anhydride; the central residue (X) was varied widely by selecting one of five neutral amino acids, two negatively chargeable moieties (aspartic and glutamic acids), and a positively chargeable species (histidine). Iontophoresis at constant current (0.36 mA/cm2), using Ag/AgCl electrodes, was conducted across freshly excised hairless mouse skin. The diffusion cells used were designed so that both anode and cathode were situated on the same (epidermal) side of a single piece of skin. Overall, it was found that the results of this research support the principle of enhanced peptide delivery across the skin by iontophoresis.
KW - Iontophoresis
KW - Peptide
KW - Percutaneous absorption
KW - Skin penetration
KW - Transdermal drug delivery
UR - http://www.scopus.com/inward/record.url?scp=0026637731&partnerID=8YFLogxK
U2 - 10.1016/0168-3659(92)90020-R
DO - 10.1016/0168-3659(92)90020-R
M3 - Article
AN - SCOPUS:0026637731
VL - 21
SP - 187
EP - 190
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1-3
ER -