INCORPORATION OF NITRIC OXIDE-RELEASING CROSS-LINKED POLYETHYLENEIMINE MICROSPHERES INTO VASCULAR GRAFTS

Over the years, many attempts have been made to increase the patency o f small-to medium-sized prosthetic vascular grafts. However, none of t hem has greatly affected long-term rates. Recently, nitric oxide (NO) has been shown to inhibit thrombus formation in such grafts, suggestin g that local delivery of NO may help to increase graft patency. This s tudy describes the site-specific delivery of NO by entrapping NO-relea sing microspheres in the pores of a vascular graft. NO-releasing polye thyleneimine microspheres (PEIX) were developed using a novel water-in -oil emulsion technique involving chemical crosslinking with a bis-epo xide. The PEIX microspheres were then derivatized with NO forming the [N(O)NO](-) moiety of the diazeniumdiolates formerly known as NONOates . These polymeric NO-releasing particles were found to spontaneously r elease 194 nmol NO/mg with a half-life of over 66 h under physiologic conditions. Fluorescein isothiocyanate-labeled microspheres were then embedded into the pores of a 60-mu m nonreinforced Gore-tex vascular g raft using a simple evacuation technique and evaluated for microsphere placement and NO release. Scanning electron microscopic analysis show ed the microspheres entrapped in the pores of the vascular graft relea sing 10 nmol NO/mg with a half-life of 51 h. The microspheres remained entrapped in the graft even after immersion and NO release, as confir med by fluorescence of the medium. These results suggest that NO-relea sing particles can be incorporated into the pores of a vascular graft to deliver therapeutic amounts of NO for the prevention of thrombosis in small-diameter prosthetic grafts. (C) 1997 John Wiley & Sons, Inc.