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Journal article
Mechanisms by Which Liposomes Improve Inhaled Drug Delivery for Alveolar Diseases
Advanced NanoBiomed Research (Online), v 3(3), 2200106
27 Jan 2023
PMID: 37266328
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Diseases of the pulmonary alveolus, such as pulmonary fibrosis, are leading causes of morbidity and mortality, but exceedingly few drugs are developed for them. A major reason for this gap is that after inhalation, drugs are quickly whisked away from alveoli due to their high perfusion. To solve this problem, the mechanisms by which nano-scale drug carriers dramatically improve lung pharmacokinetics using an inhalable liposome formulation containing nintedanib, an antifibrotic for pulmonary fibrosis, are studied. Direct instillation of liposomes in murine lung increases nintedanib's total lung delivery over time by 8000-fold and lung half life by tenfold, compared to oral nintedanib. Counterintuitively, it is shown that pulmonary surfactant neither lyses nor aggregates the liposomes. Instead, each lung compartment (alveolar fluid, alveolar leukocytes, and parenchyma) elutes liposomes over 24 h, likely serving as "drug depots." After deposition in the surfactant layer, liposomes are transferred over 3-6 h to alveolar leukocytes (which take up a surprisingly minor 1-5% of total lung dose instilled) in a nonsaturable fashion. Further, all cell layers of the lung parenchyma take up liposomes. These and other mechanisms elucidated here should guide engineering of future inhaled nanomedicine for alveolar diseases.
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Details
- Title
- Mechanisms by Which Liposomes Improve Inhaled Drug Delivery for Alveolar Diseases
- Creators
- Laura T. Ferguson - University of PennsylvaniaXiaonan Ma - University of PennsylvaniaJacob W. Myerson - Raymond and Ruth Perelman School of Medicine at the University of PennsylvaniaJichuan Wu - University of PennsylvaniaPatrick M. Glassman - Raymond and Ruth Perelman School of Medicine at the University of PennsylvaniaMarco E. Zamora - Drexel UniversityElizabeth D. Hood - Raymond and Ruth Perelman School of Medicine at the University of PennsylvaniaMichael Zaleski - Raymond and Ruth Perelman School of Medicine at the University of PennsylvaniaMengwen Shen - Yueyang HospitalEno-Obong Essien - University of PennsylvaniaVladimir V. Shuvaev - Raymond and Ruth Perelman School of Medicine at the University of PennsylvaniaJacob S. Brenner - University of Pennsylvania
- Publication Details
- Advanced NanoBiomed Research (Online), v 3(3), 2200106
- Publisher
- Wiley
- Number of pages
- 13
- Grant note
- Boehringer Ingelheim K08-HL-138269-01; T32-GM-008076 / National Heart, Lung, and Blood Institute of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) KL2TR001879 / National Center for Advancing Translational Sciences of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000921292900001
- Scopus ID
- 2-s2.0-85159778446
- Other Identifier
- 991020099056404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials
- Nanoscience & Nanotechnology