Aerosolized Liposomal Amphotericin B: A Potential Prophylaxis of Invasive Pulmonary Aspergillosis in Immunocompromised Patients

被引：12

作者：

Kamalaporn, Harutai ^{[1
]}

Leung, Kitty ^{[2
]}

Nagel, Mark ^{[3
]}

Kittanakom, Saranya ^{[4
]}

Calvieri, Battista ^{[5
]}

Reithmeier, Reinhart A. F. ^{[4
]}

Coates, Allan L. ^{[6
]}

机构：

[1] Mahidol Univ, Ramathibodi Hosp, Div Pulmonol, Dept Pediat, Bangkok 10400, Thailand

[2] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada

[3] Trudell Med Int, London, ON, Canada

[4] Univ Toronto, Dept Biochem, Toronto, ON, Canada

[5] Univ Toronto, Fac Med, Microscopy Imaging Lab, Toronto, ON, Canada

[6] Univ Toronto, Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada

来源：

PEDIATRIC PULMONOLOGY | 2014年 / 49卷 / 06期

关键词：

aerosolized liposomal amphotericin B; invasive pulmonary Aspergillosis; breath-actuated nebulizer; AeroEclipse (R); PROLONGED NEUTROPENIA; PARTICLE-SIZE; RATS; DEPOSITION; EFFICACY; DEOXYCHOLATE; NEBULIZATION; FORMULATIONS; TECHNOLOGY; NEBULIZERS;

D O I：

10.1002/ppul.22856

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

BackgroundAerosolized liposomal Amphotericin B may reduce the incidence of invasive pulmonary Aspergillosis in adults with chemotherapy-induced prolonged neutropenia with less nephrotoxicity. The breath-actuated AeroEclipse (R) BAN nebulizer is very efficient and minimizes environmental drug contamination since no aerosol is produced, unless the patient is inspiring through the device. Our aim is to develop an appropriate delivery system suitable for children that does not disrupt the liposomes due to the shear forces in nebulization. MethodsThis is an in vitro experimental study in vitro. Six ml of 4mg/ml liposomal Amphotericin B solution (AmBisome (R); Astellas Pharma Inc., Markham, Ontario, CA) was nebulized with the breath-actuated nebulizer (AeroEclipse (R); Trudell Medical International, Canada) and captured by the glass liquid impinger. Sodium dodecyl sulfate was used as detergent to disrupt the liposomes in control samples. Gel filtration, electron microscopy, and high performance liquid chromatography (HPLC) were used to compare the size and shape of the liposomes, and amount of the drug before and after nebulization. The aerosol particle size was obtained by the laser diffraction. ResultsAfter nebulization, 97.5% of amphotericin B was captured by the liquid impinger and detected by HPLC. Gel filtration and electron microscopy demonstrated that the drug remained in its liposomal configuration after nebulization. The mass median diameter (MMD) was 3.7m and 66% of aerosol particles were less than 5m in diameter. ConclusionsWe demonstrated that liposomal Amphotericin B can be nebulized successfully without disrupting the liposomes and minimize drug loss by using the breath-actuated nebulizer. Pediatr Pulmonol. 2014; 49:574-580. (c) 2013 Wiley Periodicals, Inc.

引用

页码：574 / 580

页数：7