Hoyle Gary W, Chen Jing, Schlueter Connie F, Mo Yiqun, Humphrey David M, Rawson Greg, Niño Joe A, Carson Kenneth H
Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States.
Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States.
Toxicol Appl Pharmacol. 2016 May 1;298:9-18. doi: 10.1016/j.taap.2016.03.001. Epub 2016 Mar 4.
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.
氯是一种常用的活性化合物，人类可能通过意外或故意释放而接触到它，从而导致急性肺损伤。研发了咯利普兰（一种磷酸二酯酶抑制剂）、雷公藤内酯醇（一种具有抗炎特性的天然植物产物）和布地奈德（一种皮质类固醇）的制剂，它们可以单独使用，也可以与聚乳酸-乙醇酸共聚物（PLGA）联合使用，通过肌肉注射来治疗氯诱导的急性肺损伤。这些制剂是通过喷雾干燥制备的，通常会产生适合肌肉注射的球形微粒。改变了多个参数以制备具有广泛体外释放动力学的制剂。在暴露于氯的小鼠中对选定制剂进行的测试证明了其对急性肺损伤关键方面的疗效。结果表明，开发可用于通过肌肉注射治疗氯诱导的急性肺损伤的微囊化制剂是可行的，在大规模伤亡情况下，肌肉注射是一种首选的给药途径。
