Topical disposition of two strengths of a 125I-rhEGF jelly in rat skin wounds.

Growth factors have proved to be an effective therapeutic strategy. However, some controversies have arisen concerning their efficacy in topical wound treatments. Stabilization of epidermal growth factors at the wound site and long-lasting receptor occupancy are important factors for wound repair. This study evaluated the cumulative profiles of two jellies containing 10 or 20 microg of 125I-rhEGF per gram of jelly, in a rat full-thickness skin lesion model. The prolonged time-courses at the wound sites for both strengths compared with saline solutions previously evaluated using a similar skin lesion model are reported. It seems that these two topical formulations that provide more sustained amounts of 125I-rhEGF over the period of sampling, would probably achieve the required wound healing response in terms of cell proliferation, collagen deposition and protein synthesis. Further studies need to be developed in order to elucidate whether such an in vivo disposition pattern is consistent with an earlier and stronger promotion of wound healing events.

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.