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Toxicol Appl Pharmacol ; 298: 9-18, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-26952014

RESUMO

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.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Budesonida/uso terapêutico , Cloro/toxicidade , Diterpenos/uso terapêutico , Descoberta de Drogas/métodos , Exposição por Inalação/efeitos adversos , Fenantrenos/uso terapêutico , Rolipram/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Budesonida/administração & dosagem , Budesonida/sangue , Química Farmacêutica , Diterpenos/administração & dosagem , Diterpenos/sangue , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Compostos de Epóxi/administração & dosagem , Compostos de Epóxi/sangue , Compostos de Epóxi/uso terapêutico , Injeções Intramusculares , Masculino , Camundongos Endogâmicos , Microscopia Eletrônica de Varredura , Fenantrenos/administração & dosagem , Fenantrenos/sangue , Rolipram/administração & dosagem , Rolipram/sangue , Propriedades de Superfície
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