The therapeutic delivery of NO molecules can be delayed by 'hiding' them within a block copolymer micelle.
Nitric oxide (NO) is a biological signalling molecule that, among other things, causes blood vessels to dilate, making it a useful therapy for cardiovascular conditions associated with reduced blood flow. Difficulties in delivering NO directly has led to the study of inactive 'pro-drugs' that decompose to release it after administration. These include diazeniumdiolates — also called NONOates because they contain two NO groups. Unfortunately, their use for certain post-surgery conditions is hindered by their short lifetime and rapid release of NO.
Now Jeffrey Hubbell at the Swiss Federal Institute of Technology at Lausanne and colleagues have developed1 a NONOate-based micellar delivery system that delays the release of NO. They synthesized a copolymer made up of two hydrophilic blocks, one of which reacts with NO and converts its secondary amine groups to give a hydrophobic NONOate moiety. The copolymer then forms a 50 nm micelle with the NO groups within the hydrophobic interior, thus giving them greater protection from proton-catalysed liberation.
In simple solutions, the time to release NO lengthened from half-lives of minutes and hours for related NONOate homopolymers to days for micelle-forming block copolymers. Ex vivo experiments using harvested rabbit carotid arteries showed that the micelles were able to penetrate biological tissue, indicating the potential of such NO delivery systems.
References
Jo, Y. S. et al. Micelles for delivery of nitric oxide. J. Am. Chem. Soc. 10.1021/ja905123t (2009).
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Armstrong, G. Just say NO. Nature Chem (2009). https://doi.org/10.1038/nchem.422
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DOI: https://doi.org/10.1038/nchem.422