Local Effects on Airway Inflammation and Systemic Uptake of 5nm PEG-coated and Uncoated Gold Nanoparticles in Asthmatic Mice

Nanotechnology is showing promise in many medical applications such as drug delivery and hyperthermia. Nanoparticles administered to the respiratory tract cause local reactions and cross the blood-air barrier, thereby providing a means for easy systemic administration but also a potential source of toxicity. Little is known about how these effects are influenced by pre-existing airway diseases such as asthma. Here, BALB/c mice were treated according to the OVA asthma protocol to promote allergic airway inflammation. Dispersions of polyethylene glycol (PEG)-coated and uncoated 5nm gold nanoparticles were applied intranasally to asthma and control groups and (i) airway resistance and (ii) local tissue effects measured as primary endpoints. Further, nanoparticle uptake into extrapulmonary organs was quantified by inductively-coupled plasma mass spectrometry (ICP-MS). The asthmatic precondition increased nanoparticle uptake. Moreover, systemic uptake was higher for PEG-coated gold nanoparticles compared to the uncoated particles. Nanoparticles inhibited both inflammatory infiltrates and airway hyperreactivity, especially uncoated gold nanoparticles. Although the anti-inflammatory effects of gold nanoparticles might be of therapeutic benefit, systemic uptake and consequent adverse effects must be considered when designing and testing nanoparticle-based asthma therapies.