用于吸入递送抗假单胞菌抗生素的微粒
Microparticles for inhalational delivery of antipseudomonal antibiotics.
作者信息
Tsifansky Michael D, Yeo Yoon, Evgenov Oleg V, Bellas Evangelia, Benjamin John, Kohane Daniel S
机构信息
Department of Pediatrics, Division of Pediatric Intensive Care Medicine, Lutheran General Children's Hospital, 1775 Dempster St., Park Ridge, Illinois, 60068, USA.
出版信息
AAPS J. 2008 Jun;10(2):254-60. doi: 10.1208/s12248-008-9033-8. Epub 2008 May 3.
Chronic pseudomonal bronchopulmonary infections in cystic fibrosis patients are frequently controlled with inhaled antibiotics. Dry-powder inhalable antibiotics are an attractive alternative to nebulized medications. We produced and evaluated microparticles composed of dipalmitoylphosphatidylcholine, albumin, and lactose as a model system for intrapulmonary delivery of ceftazidime, ciprofloxacin, and several combinations of the two, none of which is presently available for inhalation. Microparticles containing one or both antibiotics were prepared by spray-drying. Their Anderson cascade impactor deposition profiles showed 10-30% fine particle fractions of the nominal dose. Microparticles containing varying amounts of each antibiotic showed statistically different deposition profiles. Aerodynamics and deposition of microparticles co-encapsulating both antibiotics were similar to those of single-drug microparticles with the same proportion of ciprofloxacin alone. The antipseudomonal activities of microparticles co-encapsulating half of the 50% effective concentration (EC(50)) of both ceftazidime and ciprofloxacin (5 mg of particles containing 5% ceftazidime and 10% ciprofloxacin) were at least additive compared to particles containing the EC(50) of each antibiotic separately (5 mg of particles containing 10% ceftazidime or 5 mg of particles containing 20% ciprofloxacin). Co-encapsulation of the antibiotics in microparticles ensures co-deposition at desired ratios, improves the particles' aerodynamics and fine particle fraction, as compared to microparticles with equivalent amounts of ceftazidime alone, and achieves additive antipseudomonal activity.
囊性纤维化患者的慢性铜绿假单胞菌支气管肺部感染通常采用吸入性抗生素进行控制。干粉吸入性抗生素是雾化药物的一种有吸引力的替代方案。我们制备并评估了由二棕榈酰磷脂酰胆碱、白蛋白和乳糖组成的微粒,作为头孢他啶、环丙沙星以及两者几种组合的肺内递送模型系统,目前这些组合均无吸入剂型。通过喷雾干燥制备了含有一种或两种抗生素的微粒。它们的安德森级联撞击器沉积曲线显示,标称剂量的细颗粒分数为10%-30%。含有不同量每种抗生素的微粒显示出统计学上不同的沉积曲线。共包封两种抗生素的微粒的空气动力学和沉积情况与单独含有相同比例环丙沙星的单药微粒相似。与分别含有每种抗生素50%有效浓度(EC50)的微粒(5mg含有10%头孢他啶的微粒或5mg含有20%环丙沙星的微粒)相比,共包封头孢他啶和环丙沙星50%有效浓度一半的微粒(5mg含有5%头孢他啶和10%环丙沙星的微粒)的抗铜绿假单胞菌活性至少具有相加性。将抗生素共包封在微粒中可确保按所需比例共同沉积,与仅含有等量头孢他啶的微粒相比,改善了微粒的空气动力学和细颗粒分数,并实现了相加的抗铜绿假单胞菌活性。