Invitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-doped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive
Open accessAbstract
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.
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Handa et al. and Cai et al. studied PLGA additives with different hydrolysis rates to slowly generate protons in the organic polymer phase and drive NO release from NONOates.
“Therefore, Handa et al.154,155 as well as Cai et al.156 studied various poly(lactic-co-glycolic acid) (PLGA) additives with different hydrolysis rates as a means to slowly produce protons within the organic polymer phase that can continue to drive NO release reaction from NONOates.”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [154]
Handa et al.'s ECC tubing composed of 25 wt% DBHD/N2O2 and 10 wt% PLGA additives in a 2:1 PVC/DOS polymer matrix achieved up to 14 d of NO release between 7-18 × 10−10 mol cm−2 min−1 at 37 °C.
“Handa et al. recently prepared ECC tubing composed of 25 wt% DBHD/N2O2 and 10 wt% PLGA (5050DLG7E) additives in 2:1 PVC/DOS polymer matrix and achieved up to 14 d of NO release between 7–18 × 10−10 mol cm−2 min−1 at 37 °C.154”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [154]
This circuit tubing preserved platelet count during 4 h experiments, with 79 ± 11% versus 54 ± 6% for NO release circuits compared with PVC/DOS controls.
“This circuit tubing successfully preserved the platelet count during 4 h of experiments, with 79 ± 11 % vs. 54 ± 6 % for the NO release circuits compared to PVC/DOS controls.”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [154]
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- Authors
- Handa, H., Brisbois, E. J., Major, T. C., Refahiyat, L., Amoako, K. A., Annich, G. M., Bartlett, R. H., & Meyerhoff, M. E.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Meyerhoff, Mark E.
- ORCID
- Venue
- Journal of Materials Chemistry B
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2013
- Volume
- 1
- Issue
- 29
- Pages
- 3578
- ISSN
- 2050-750X (ISSN-L)
- 2050-7518
- PMC
- PMC3728720
- OpenAlex
- W2157867691
- Cited by
- 64
- References
- 41
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 11 · 2016: 9 · 2015: 6 · 2014: 8 · 2013: 1
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Materials Chemistry B (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons - New Heaven (University of New Haven) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL069420, K25HL111213)
- National Institute of Biomedical Imaging and Bioengineering (R01EB000783)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD015434)
- Topics
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Physical Sciences › Materials Science › Polymers and Plastics › Polymer Science and PVC
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nitric oxide release, diazeniumdiolates, poly(lactic-co-glycolic acid), sustained drug release, pH-dependent release, extracorporeal circulation, thrombogenicity, platelet adhesion, antithrombotic coatings, hemodynamics
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