Chemical and biological assessment of metal organic frameworks (MOFs) in pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial hypertension therapy:

摘要: Pulmonary arterial hypertension (PAH) is a progressive and debilitating condition. Despite promoting vasodilation, current drugs have therapeutic window within which they are limited by systemic side effects. Nanomedicine uses nanoparticles to improve drug delivery and/or reduce We hypothesize that this approach could be used deliver PAH avoiding the circulation. Here we report use of iron metal organic framework (MOF) MIL-89 PEGylated (MIL-89 PEG) as suitable carriers for drugs. assessed their effects on viability inflammatory responses in wide range lung cells including endothelial grown from blood donors with/without PAH. Both MOFs conformed predicted structures with PEG being more stable at room temperature. At concentrations up 10 or 30 µg/mL, toxicity was only seen pulmonary artery smooth muscle where both reduced cell CXCL8 release. In control patients, preparations inhibited release endothelin-1 macrophages inducible nitric oxide synthase activity. Finally, well-tolerated accumulated rat lungs when given in vivo. Thus, prototypes core capacity accommodate relatively non-toxic may added advantage anti-inflammatory reducing endothelin-1. These data consistent idea these materials not useful but also offer some benefit own right.