Development of Aerosol Phospholipid Microparticles for the Treatment of Pulmonary Hypertension
Autor: | Zimeng Wang, Samantha A. Meenach, Sarah Brousseau, Sweta K. Gupta |
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Rok vydání: | 2017 |
Předmět: |
Drug
Cell Survival Hypertension Pulmonary media_common.quotation_subject Phospholipid Pharmaceutical Science 02 engineering and technology Aquatic Science Pharmacology 030226 pharmacology & pharmacy Excipients 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Administration Inhalation Drug Discovery medicine Humans Particle Size Phospholipids Ecology Evolution Behavior and Systematics media_common Aerosols Lung Dose-Response Relationship Drug Ecology Chemistry Dry Powder Inhalers General Medicine 021001 nanoscience & nanotechnology medicine.disease Pulmonary hypertension Microspheres Bioavailability Aerosol Treatment Outcome medicine.anatomical_structure A549 Cells Dipalmitoylphosphatidylcholine Spray drying 0210 nano-technology Agronomy and Crop Science |
Zdroj: | AAPS PharmSciTech. 18:3247-3257 |
ISSN: | 1530-9932 |
Popis: | 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. |
Databáze: | OpenAIRE |
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