title: Treatment of respiratory damage in mice by aerosols of drug-encapsulating targeted lipid-based particles.
abstract: 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 2week period were applied, deliberately, as a non-invasive clinical parameter. Control mice gained weight continuously, whereas a non-lethal 30minute exposure of mice to 300ppm Cl2in 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ilia
authors.initials: I
authors.lastname: Rivkin
authors.affiliation: Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yifat
authors.initials: Y
authors.lastname: Galnoy-Glucksam
authors.affiliation: Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Inbar
authors.initials: I
authors.lastname: Elron-Gross
authors.affiliation: NBC Protection Division, IMOD, The Hebrew University, Jerusalem, Israel.
authors.forename: Amichay
authors.initials: A
authors.lastname: Afriat
authors.affiliation: NBC Protection Division, IMOD, The Hebrew University, Jerusalem, Israel; IDF Medical Corps, The Hebrew University, Jerusalem, Israel; The Institute for Research in Military Medicine, The Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
authors.forename: Arik
authors.initials: A
authors.lastname: Eisenkraft
authors.affiliation: Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. Electronic address: rimona@post.tau.ac.il.
authors.forename: Rimona
authors.initials: R
authors.lastname: Margalit
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry*; D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005100:Expectorants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009330:Nebulizers and Vaporizers; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000336:Aerosols; D005100:Expectorants; D005938:Glucocorticoids; D008081:Liposomes; D003907:Dexamethasone; D000111:Acetylcysteine
keywords: Aerosols; Mass casualty events; Respiratory damage; TIC exposure