Development of Aerosol Phospholipid Microparticles for the Treatment of Pulmonary Hypertension

被引:0
作者
Sarah Brousseau
Zimeng Wang
Sweta K. Gupta
Samantha A. Meenach
机构
[1] University of Rhode Island,Department of Chemical Engineering
[2] University of Rhode Island,Department of Biomedical and Pharmaceutical Sciences
来源
AAPS PharmSciTech | 2017年 / 18卷
关键词
pulmonary arterial hypertension; microparticles; aerosol delivery; spray drying; phospholipid;
D O I
暂无
中图分类号
学科分类号
摘要
Pulmonary arterial hypertension (PAH) is an incurable cardiovascular disease characterized by high blood pressure in the arteries leading from the heart to the lungs. Over two million people in the USA are diagnosed with PAH annually and the typical survival rate is only 3 years after diagnosis. Current treatments are insufficient because of limited bioavailability, toxicity, and costs associated with approved therapeutics. Aerosol delivery of drugs is an attractive approach to treat respiratory diseases because it increases localized drug concentration while reducing systemic side effects. In this study, we developed phospholipid-based aerosol microparticles via spray drying consisting of the drug tacrolimus and the excipients dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol. The phospholipid-based spray-dried aerosol microparticles were shown to be smooth and spherical in size, ranging from 1 to 3 μm in diameter. The microparticles exhibited thermal stability and were amorphous after spray drying. Water content in the microparticles was under 10%, which will allow successful aerosol dispersion and long-term storage stability. In vitro aerosol dispersion showed that the microparticles could successfully deposit in the deep lung, as they exhibited favorable aerodynamic diameters and high fine particle fractions. In vitro dose-response analysis showed that TAC is nontoxic in the low concentrations that would be delivered to the lungs. Overall, this work shows that tacrolimus-loaded phospholipid-based microparticles can be successfully created with optimal physicochemical and toxicological characteristics.
引用
收藏
页码:3247 / 3257
页数:10
相关论文
共 133 条
[1]  
Archer S(2010)Basic science of pulmonary arterial hypertension for clinicians new concepts and experimental theories Circulation 121 2045-U175
[2]  
Weir E(2013)Development of controlled release inhalable polymeric microspheres for treatment of pulmonary hypertension Int J Pharm 450 114-122
[3]  
Wilkins M(2004)Cellular and molecular pathobiology of pulmonary arterial hypertension J am Coll Cardiol 43 S13-S24
[4]  
Saigal A(2013)FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension J Clin Investig 123 3600-3613
[5]  
Ng WK(2006)Particle engineering techniques for inhaled biopharmaceuticals Adv Drug Deliv rev 58 1009-1029
[6]  
Tan RBH(2013)Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols Int J Nanomedicine 8 275-293
[7]  
Chan SY(2001)Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance J Control Release 70 329-339
[8]  
Humbert M(2003)Control of the morphology of nanostructured particles prepared by the spray drying of a nanopartcile sol J Colloid Interface Sci 265 296-303
[9]  
Morrell NW(2014)Use of a fundamental approach to spray-drying formulation design to facilitate the development of multi-component dry powder aerosols for respiratory drug delivery Pharm res 31 449-465
[10]  
Archer SL(2014)High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: physiochemical characterization, in vitro aerosol dispersion, and cellular studies AAPS PharmSciTech 15 1574-1587