Local delivery of nitric oxide: Targeted delivery of therapeutics to bone and connective tissues

Abstract

Non-invasive treatment of injuries and disorders affecting bones and connective tissue is a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several 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.

Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO)

“…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 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 This low bioavailability limits nitroglycerin’s use as an efficient NO donor and complicates clinical treatments.…”

“…Many different metal NO complexes have been reported, including manganese, 108,136 iron 144 and ruthenium-NO 108,111,136 complexes, with sodium nitroprusside (Na 2 [Fe(CN) 5 NO], SNP) being the most common. SNP is often used as a potent vasodilator in hypertensive emergencies, 144 which releases NO in the presence of reducing agents (e.g., thiol-containing compounds such as cysteine or glutathione) or by illumination with near-infrared or visible light.…”

“…111,120,144 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 …”

Combination of nitric oxide and drug delivery systems: tools for overcoming drug resistance in chemotherapy

“…As the complicated functions of NO are highly dependent on its concentration and duration [28], NO delivery systems that can deliver NO donors to the target sites and control the NO release are prerequisite to realize the full potential of NO [34]. Current progress of NO delivery systems is summarized in details in references 31–34.…”

Síntese e caracterização de nanopartículas magnéticas: Aplicação como vetores de liberação de óxido nítrico

“…O uso potencial do NO para tratar lesão no tendão, apresenta a necessidade de controlar concentrações localizadas de NO para promover e não inibir a deposição de colágeno. Uma solução de albumina de soro bovino nitrosada tem sido utilizada como carreadora e liberadora de NO [66].…”