Abstract

Nitric oxide (NO) is a highly potent radical with a wide spectrum of physiological activities. Depending on the concentration, it can enhance endothelial cell proliferation in a growth factor‐free medium, mediate angiogenesis, accelerate wound healing, but may also lead to tumor progression or induce inflammation. Due to its multifaceted role, NO must be administered at a right dose and at the specific site. Many efforts have focused on developing NO‐releasing biomaterials; however, NO short half‐life in human tissues only allows this molecule to diffuse over short distances, and significant challenges remain before the full potential of NO can be realized. Here, an overview of platforms that are engineered to release NO via catalytic or noncatalytic approaches is presented, with a specific emphasis on progress reported in the past five years. A number of NO donors, natural enzymes, and enzyme mimics are highlighted, and recent promising developments of NO‐releasing scaffolds, particles, and films are presented. In particular, key parameters of NO delivery are discussed: 1) NO payload, 2) maximum NO flux, 3) NO release half‐life, 4) time required to reach maximum flux, and 5) duration of NO release. Advantages and drawbacks are reviewed, and possible further developments are suggested.

Highlights

  • Nitric oxide (NO) as a signaling molecule in the cardiovascular system

  • We highlighted NO release parameters (NO payload, maximum NO flux, NO release half-life, time required to reach maximum flux, and duration of NO release), at times it is still challenging to compare the parameters between studies due to irregular reporting

  • Thorough characterizations must remain at the forefront of NO efficacy studies

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Summary

NO Delivery from Small Molecule NO Donors

NO donors are pharmacologically active substances that carry NO and stabilize the radical until release is required. Tao is a Ph.D. student under the supervision of Dr Rona Chandrawati at The University of New South Wales, Sydney, Australia. Dr Rona Chandrawati obtained her Ph.D. from the Department of Chemical and Biomolecular Engineering at The University of Melbourne in 2012. She was a Marie Curie Fellow at Imperial College London prior to joining The University of Sydney as a Lecturer (Assistant Professor) in 2015. The clinical applications of low molecular weight NO donors have been restricted due to issues such as burst release and nontargeted delivery. Their encapsulation in carriers enabled controlled and sustained delivery of NO. A majority of studies on NO delivery from injectable materials to date have focused on their efficacy against bacteria and biofilms in vitro

Liposomes
Micelles
Dendrimers
Silica and Gold Nanoparticles
Polymer Particles
Metal–Organic Frameworks
NO Delivery from Implantable Materials
NO Delivery via Catalytic Approaches
Localized Synthesis of NO Using Natural Enzymes and Synthetic Prodrugs
Enzyme Mimics for Conversion of Endogenous Prodrugs of NO
Conclusions and Future Perspectives
Findings
Conflict of Interest
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