Credit: © 2009 ACS

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.