title: Development and assessment of countermeasure formulations for treatment of lung injury induced by chlorine inhalation.
abstract: Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation.
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States. Electronic address: Gary.Hoyle@louisville.edu.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Hoyle
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States.
authors.forename: Connie F
authors.initials: CF
authors.lastname: Schlueter
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Mo
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Humphrey
authors.affiliation: Microencapsulation and Nanomaterials Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX, United States.
authors.forename: Greg
authors.initials: G
authors.lastname: Rawson
authors.affiliation: Microencapsulation and Nanomaterials Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX, United States.
authors.forename: Joe A
authors.initials: JA
authors.lastname: Niño
authors.affiliation: Microencapsulation and Nanomaterials Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX, United States.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Carson
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D019819:Budesonide / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D002713:Chlorine / Q000633:toxicity*; D004224:Diterpenes / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry; D055808:Drug Discovery / Q000379:methods*; D065546:Drug Liberation; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D019570:Inhalation Exposure / Q000009:adverse effects*; D007273:Injections, Intramuscular; D008297:Male; D008815:Mice, Inbred Strains; D008855:Microscopy, Electron, Scanning; D010616:Phenanthrenes / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D020889:Rolipram / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013499:Surface Properties
chemical_list: D004224:Diterpenes; D004337:Drug Carriers; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide; D002713:Chlorine; D019819:Budesonide; D020889:Rolipram
keywords: Acute lung injury; Airway hyperreactivity; Microencapsulation; Pulmonary edema