Inhalable Advanced Co-Spray Dried Microparticles/Nanoparticles of a Novel RhoA/Rho Kinase Inhibitor with Lung Surfactant Biomimetic Phospholipids for Targeted Lung Delivery.

Autor:	Ruiz VH; The University of Arizona College of Pharmacy, Skaggs Pharmaceutical Sciences Center, Tucson, Arizona85721, United States., Encinas-Basurto D; The University of Arizona College of Pharmacy, Skaggs Pharmaceutical Sciences Center, Tucson, Arizona85721, United States.; University of Sonora, Sonora, Mexico. 83304, United States., Ortega-Alarcon N; The University of Arizona College of Pharmacy, Skaggs Pharmaceutical Sciences Center, Tucson, Arizona85721, United States., Eedara BB; The University of Arizona College of Pharmacy, Skaggs Pharmaceutical Sciences Center, Tucson, Arizona85721, United States.; Center for Translational Science, Florida International University, Port St. Lucie, Florida 34987, United States., Fineman JR; Department of Pediatrics, University of California San Francisco School of Medicine, San Francisco, California 94143, United States., Black SM; Center for Translational Science, Florida International University, Port St. Lucie, Florida 34987, United States.; Department of Medicine, Division of Translational and Regenerative Medicine, The University of Arizona College of Medicine, Tucson Arizona 85721, United States., Mansour HM; The University of Arizona College of Pharmacy, Skaggs Pharmaceutical Sciences Center, Tucson, Arizona85721, United States.; Center for Translational Science, Florida International University, Port St. Lucie, Florida 34987, United States.; Department of Medicine, Division of Translational and Regenerative Medicine, The University of Arizona College of Medicine, Tucson Arizona 85721, United States.; BIO5 Institute, The University of Arizona, Tucson, Arizona 85721, United States.
Jazyk:	angličtina
Zdroj:	ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2024 Oct 03; Vol. 7 (10), pp. 3241-3254. Date of Electronic Publication: 2024 Oct 03 (Print Publication: 2024).
DOI:	10.1021/acsptsci.4c00432
Abstrakt:	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. Competing Interests: The authors declare no competing financial interest. (© 2024 American Chemical Society.)
Databáze:	MEDLINE
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