Disposition and receptor-site binding of (125)I-EGF after topical administration to skin wounds.
The rhEGF topical delivery systems have been hindered by a number of shortcomings which have led to the search of new development strategies. In this study we report the evaluation of cumulative profiles of 10, 5 and 1 microg/ml solutions of (125)I-rhEGF, in a rat full-thickness skin wound model, as well as the drug-induced modulation in the expression of the EGF receptor after lesion. The tissue-associated radioactivity, expressed as the percentage of the dose administered per grams of tissue (%D/g), peaks at 2 h after administration of all doses. (125)I-rhEGF degraded species were detected chromatographically, but no diffusion of the peptide to the surrounding skin was documented. Despite the dose, the EGF receptor expression was increased within 2 h after wounding, followed by a slow decline up to 12 h below baseline. Twelve hours after punch, differences were evident between all treated groups and control. These results demonstrate that (125)I-rhEGF saline solutions are rapidly cleared from application sites, probably by protease-driven cleavage and receptor-mediated endocytosis. Finally, we must be aware that the results herein discussed should be taken into account during the drug delivery system design in order to guarantee the necessary steady-state rhEGF levels upon wound healing process.
Prats
P A
PA
Department of Pharmacology and Toxicology, Center for Genetic Engineering and Biotechnology, Havana, Ave 31 e/ 158 y 190, P.O. Box 6162, Havana 10600, Cuba.
Duconge
J
J
Valenzuela
C
C
Berlanga
J
J
Edrosa
C R
CR
Fernández-Sánchez
E
E
D000287:Administration, Topical; D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D004058:Diffusion; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D011869:Radioligand Assay; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D012867:Skin / Q000293:injuries*; D012869:Skin Absorption
D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors