Disposition and receptor‐site binding of ¹²⁵I‐EGF after topical administration to skin wounds

Abstract

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.

Epidermal growth factor prevents prepartum luteolysis in the rat

“…The idea of a direct action on rat luteal cells is reinforced by the demonstration of high-affinity, low-capacity EGF-binding sites in these cells (38). On the other hand, EGF peptide is rapidly degraded after in vivo administration (39,40). We demonstrated that EGF is exerting its effect through the second mechanism.…”

Type 2 Diabetes Mellitus (T2DM): Biological Overview from Pathways to Organelles and its Translation toward a Torpid Wound Healing Process

“…It was somewhat surprising as other studies had already established proteolysis on GFs and their receptors in chronicity circumstances [133]. Further evaluations of cumulative profiles of radiolabeled EGF in a rat full-thickness wound model showed EGF degraded subspecies and a short residence time within the wound contours [134]. We had the experience of injecting EGF locally into denervated rat hind limbs upon sciatic nerve full-thickness cut.…”

Targeting cytokine/chemokine receptors: a challenge for molecular nuclear medicine

“…125 I-labelled tumour growth factor beta (TGF-β) has been used for the study of angiogenesis [30] and radiolabelled epidermal growth factor (EGF) has been used for the study of metastatic lymph nodes, for imaging breast cancer and for the study of skin wounds [31,32,33]. Most radiolabelled cytokines have been used for the study of inflammatory diseases, e.g.…”