title: In vitroandin vivostudy of sustained nitric oxide release coating using diazeniumdiolate-oped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive.
abstract: Nitric oxide (NO) is an endogenous vasodilator as well as natural inhibitor of platelet adhesion and activation that can be released from a NO donor species, such as diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) within a polymer coating. In this study, various Food and Drug Administration approved poly(lactic-co-glycolic acid) (PLGA) species were evaluated as additives to promote a prolonged NO release from DBHD/N2O2within a plasticized poly(vinyl chloride) (PVC) matrix. When using an ester-capped PLGA additive with a slow hydrolysis time, the resulting coatings continuously release between 7-18×10-10mol cm-2min-1NO for 14 d at 37°C in PBS buffer. The corresponding pH changes within the polymer films were visualized using pH sensitive indicators and are shown to correlate with the extended NO release pattern. The optimal combined diazeniumdiolate/PLGA-doped NO release (NOrel) PVC coating was evaluatedin vitroand its effect on the hemodynamics was also studied within a 4 hin vivoextracorporeal circulation (ECC) rabbit model of thrombogenicity. Four out of 7 control circuits clotted within 3 h, whereas all the NOrel coated circuits were patent after 4 h. Platelet counts on the NOrel ECC were preserved (79 ± 11% compared to 54 ± 6% controls). The NOrel coatings showed a significant decrease in the thrombus area as compared to the controls. Results suggest that by using ester-capped PLGAs as additives to a conventional plasticized PVC material containing a lipophilic diazeniumdiolates, the NO release can be prolonged for up to 2 weeks by controlling the pH within the organic phase of the coating.
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI USA.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Handa
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Brisbois
authors.forename: Terry C
authors.initials: TC
authors.lastname: Major
authors.forename: Lahdan
authors.initials: L
authors.lastname: Refahiyat
authors.forename: Kagya A
authors.initials: KA
authors.lastname: Amoako
authors.forename: Gail M
authors.initials: GM
authors.lastname: Annich
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bartlett
authors.forename: Mark E
authors.initials: ME
authors.lastname: Meyerhoff
keywords: Diazeniumdiolate; Extracorporeal Circulation; Nitric Oxide; PLGA; Platelets
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