Effects of pH, electric current, and enzyme inhibitors on iontophoresis of delta sleep-inducing peptide.
Delta sleep-inducing peptide (DSIP), a peptide of nine amino acid residues, was used as a model drug to investigate the effects of pH, electric current, and enzyme inhibitors on the transdermal iontophoretic delivery of peptide drugs. DSIP was fairly stable in pH 4-9 buffer solutions but was cleaved by the skin enzymes during iontophoretic delivery. Enzyme inhibitors, such as o-phenanthroline, ethylene-diaminetetraacetic acid (EDTA), dilucine, and sodium deoxycholate, could inhibit the degradation of DSIP to a certain extent in the skin homogenate. Our results showed that metalloproteases were probably more important enzymes for DSIP hydrolysis. By using 0.2 mM o-phenanthroline in the iontophoretic delivery of DSIP at pH 4, we were able to significantly enhance the penetration of DSIP. The flux was about eight times as much as control (without o-phenanthroline) at pH 7.4.
Chiang
C H
CH
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Shao
C H
CH
Chen
J L
JL
D000279:Administration, Cutaneous; D000818:Animals; D003701:Delta Sleep-Inducing Peptide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004355:Drug Stability; D004560:Electricity; D005069:Evaluation Studies as Topic; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods*; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D010618:Phenanthrolines / Q000008:administration & dosage; D011480:Protease Inhibitors / Q000008:administration & dosage; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D010618:Phenanthrolines; D011480:Protease Inhibitors; D003701:Delta Sleep-Inducing Peptide; D008666:Metalloendopeptidases; C025205:1,10-phenanthroline