Victor H. Ruiz, David Encinas-Basurto, Neftali Ortega-Alarcon, Basanth Babu Eedara, Jeffrey R. Fineman, Stephen M. Black, Heidi M. Mansour
University of Arizona College of Pharmacy, University of Arizona College of Medicine and University of Arizona. University of Sonora. Florida International University. University of California San Francisco School of Medicine.
United States and Mexico
American Chemical Society Pharmacology and Translational Science
ACS Pharmacol Transl Sci 2024;
DOI: 10.1021/acsptsci.4c00432
Abstract
Co-spray dried inhalable powder formulations of fasudil monohydrochloride salt (FMCS) and inhalable lung surfactant-based nanocarriers composed of synthetic phospholipids, zwitterionic DPPC (1,2-palmitoyl-sn-glycero-3-phosphocholine) and anionic DPPG (1,2-dipalmitoyl-sn-glycero-3-[phosphor-rac-1-glycerol]) sodium salt, were designed and optimized using organic solution advanced spray drying. FMCS can potentially be used for the treatment of various complex pulmonary diseases with this current work focusing on pulmonary arterial hypertension. Comprehensive physicochemical characterization, electron and optical microscopy imaging, thermal analysis, molecular fingerprinting spectroscopy, in vitro aerosol dispersion performance with human dry powder inhaler (DPI) devices, in vitro membrane permeation and drug release, and in vitro human cellular studies were conducted. Well-defined, small, and smooth nanoparticles/microparticles in the solid state were engineered at different molar ratios of FMCS/DPPC/DPPG (25:75, 50:50, and 75:25) and successfully produced as inhalable powders having the properties necessary for targeted pulmonary delivery as dry powder inhalers. In vitro aerosol performance demonstrated excellent aerosol dispersion with different DPI devices. The phospholipid bilayer biophysical properties were confirmed and retained following cospray drying. Sustained release of fasudil drug and in vitro biocompatibility were demonstrated on human lung cells from different airway regions.
Category
Medical Therapy. Pharmacokinetics and Pharmacology
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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Free PDF File or Full Text Article Available Through PubMed or DOI: Yes, after October 3, 2025