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

被引:53
作者
Handa, Hitesh [1 ]
Brisbois, Elizabeth J. [2 ]
Major, Terry C. [1 ]
Refahiyat, Lahdan [2 ]
Amoako, Kagya A. [1 ]
Annich, Gail M. [3 ]
Bartlett, Robert H. [1 ]
Meyerhoff, Mark E. [2 ]
机构
[1] Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Pediat & Communicable Dis, Med Ctr, Ann Arbor, MI 48109 USA
基金
美国国家卫生研究院;
关键词
BLOOD COMPATIBILITY; EXTRACORPOREAL-CIRCULATION; MICROCLIMATE PH; PLATELET; DEGRADATION; ACTIVATION; HEMOCOMPATIBILITY; THROMBOSIS; DELIVERY; NO;
D O I
10.1039/c3tb20277a
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
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 x 10(-10) mol cm(-2) min(-1) NO for 14 days at 37 degrees 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.
引用
收藏
页码:3578 / 3587
页数:10
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