Treatment of respiratory damage in mice by aerosols of drug-encapsulating targeted lipid-based particles

The purpose of this study was to develop a treatment for respiratory damage caused by exposure to toxic industrial chemicals (TICs), including mass casualty events, by aerosols of dexamethasone and/or N-acetyl cysteine formulated in targeted lipid-based particles. Good encapsulation, performance as slow-release drug depots, conservation of matter, and retention of biological activity were obtained for the three drug-carrier formulations, pre- and post-aerosolization. Weight changes over a 2 week period were applied, deliberately, as a non-invasive clinical parameter. Control mice gained weight continuously, whereas a non-lethal 30 minute exposure of mice to 300 ppm Cl2 in air showed a two-trend response. Weight loss over the first two days, reversing thereafter to weight gain, but at a rate and level significantly slower and smaller than those of the control mice, indicating the chlorine damage was long-term. The weight changes of Cl2-exposed mice given the inhalational treatments also showed the two-trend response, but the weight gain rates and levels were similar to those of the control mice, reaching the weight-gain range of the control mice. Following this proof of concept, studies are now extended to include additional TICs, and biochemical markers of injury and recovery.

A. The experimental set-up. B. Impact of the liposomal inhalational treatment on chlorine-exposed mice at day 2 and day 4 from exposure and therapy.185