Local delivery of nitric oxide: Targeted delivery of therapeutics to bone and connective tissues
Open accessAbstract
Non-invasive treatment of injuries and disorders affecting bone and connective tissue remains a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several important roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair.
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Nitroglycerin releases one mole equivalent of NO upon bioactivation by mitochondrial aldehyde dehydrogenase.
“Nitroglycerin, the most commonly used organic nitrate for clinically treating hypertension and angina pain, is known to release 1 mole equivalent of NO upon bioactivation by mitochondrial aldehyde dehydrogenase (mtALDH).111”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [111]
Prolonged nitroglycerin use often causes nitrate tolerance because reactive oxygen species oxidize the thiol group of mtALDH and cause enzyme dysfunction.
“However, patients often develop nitrate tolerance (tachyphylaxis) after prolonged use because the reactive oxygen species generated by nitroglycerin can oxidize the thiol group of the mtALDH and result in enzyme dysfunction.111,141–143”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [111]
Cellular toxicity concerns from cyanide and cytotoxic peroxynitrite byproducts make metal nitrosyl complexes less attractive as medicinal NO donors.
“However, cellular toxicity concerns due to the release of cyanide and cytotoxic peroxynitrite as byproducts have made metal nitrosyl complexes less attractive as medicinally used NO donors.111,140”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [111]
NO has antimicrobial activity against a growing list of microorganisms, including bacteria, fungi, parasites, viruses, and yeast.
“Nitric oxide (NO) has antimicrobial activity against a growing list of microorganisms, including bacteria, fungi, parasites, viruses, and yeast.20,111,120,127,177,281,282”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [111]
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References 170 · Cited by 148
- Authors
- Nichols, S. P., Storm, W. L., Koh, A., & Schoenfisch, M. H.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Schoenfisch, Mark H.
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 64
- Issue
- 12
- Pages
- 1177-1188
- ISSN
- 0169-409X (ISSN-L)
- PMC
- PMC3383916
- OpenAlex
- W2071373598
- Cited by
- 148
- References
- 170
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 5 · 2023: 13 · 2022: 13 · 2021: 19 · 2020: 7 · 2019: 14 · 2018: 12 · 2017: 8 · 2016: 11 · 2015: 9 · 2014: 6 · 2013: 8 · 2012: 2
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (EB 000708, R01EB000708)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nitric oxide, nitric oxide donors, local drug delivery, bone regeneration, connective tissue repair, skin wound healing, tendon repair, non-invasive treatment, bone tissue engineering
- MeSH terms
- Animals, Bone and Bones, Connective Tissue, Humans, Nitric Oxide, Skin, Tendons, Wound Healing, Drug Delivery Systems, Nitric Oxide Donors
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