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Issue 29, 2013
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Invitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-doped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive

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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/N2O2 within 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 and 18 × 10−10 mol cm−2 min−1 NO for 14 days 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 evaluated in vitro and its effect on the hemodynamics was also studied within a 4 h in vivo extracorporeal 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 lipophilic diazeniumdiolates, the NO release can be prolonged for up to 2 weeks by controlling the pH within the organic phase of the coating.

Graphical abstract: In vitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-doped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive

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Publication details

The article was received on 27 Feb 2013, accepted on 30 May 2013 and first published on 03 Jun 2013


Article type: Paper
DOI: 10.1039/C3TB20277A
J. Mater. Chem. B, 2013,1, 3578-3587

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    In vitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-doped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive

    H. Handa, E. J. Brisbois, T. C. Major, L. Refahiyat, K. A. Amoako, G. M. Annich, R. H. Bartlett and M. E. Meyerhoff, J. Mater. Chem. B, 2013, 1, 3578
    DOI: 10.1039/C3TB20277A

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