Local infusion of FGF-saporin reduces intimal hyperplasia

The Journal of Surgical Research
S G MattarA B Lumsden

Abstract

The recent conjugation of the potent ribosome-inactivating protein saporin (SAP) with basic fibroblast growth factor (FGF2) to form recombinant (r)FGF2-SAP permits increased selectivity of this mitoxin for cells exhibiting upregulated FGF receptors. Systemic administration of rFGF-SAP in therapeutic doses, however, may be associated with significant liver toxicity. In this blinded study, we used a local boundary layer infusion approach to increase local drug concentration while minimizing the risk of side effects. Six dogs underwent bilateral carotid endarterectomies. Expanded polytetrafluoroethylene infusion devices, blindly primed with rFGF2-SAP to one artery or vehicle to the contralateral vessel, were anastomosed proximal to the injured segments so that each animal served as its own control. rFGF2-SAP (2 microgram/kg/day) or vehicle (5 microl/hr) was continuously delivered for 14 days from an osmotic reservoir, through the wall of the graft infusion device. Euthanasia was carried out at 14 days and the processed arteries were blindly analyzed for intimal thickening and cellular proliferation. All dogs survived until sacrifice with no clinical side effects. Liver function tests at euthanasia were not significantly altered wh...Continue Reading

Citations

Apr 16, 2014·Journal of Biomedical Materials Research. Part a·Mirhamed HajimiriRassoul Dinarvand
Nov 6, 2002·Journal of Biomedical Materials Research·Camiel C L PeerlingsLeo H Koole
Dec 27, 1996·The Journal of Biological Chemistry·B A SosnowskiA Baird
Dec 6, 2001·Journal of Controlled Release : Official Journal of the Controlled Release Society·I FishbeinG Golomb
Jun 6, 2000·Advanced Drug Delivery Reviews·W A Marasco, Dana Jones S

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