@article{086eec1bcf064ae7a4ff2959976b4cea,
title = "Advanced Microparticulate/Nanoparticulate Respirable Dry Powders of a Selective RhoA/Rho Kinase (Rock) Inhibitor for Targeted Pulmonary Inhalation Aerosol Delivery",
abstract = "Pulmonary hypertension (PH) is a progressive disease that eventually leads to heart failure and potentially death for some patients. There are many unique advantages to treating pulmonary diseases directly and non-invasively by inhalation aerosols and dry powder inhalers (DPIs) possess additional unique advantages. There continues to be significant unmet medical needs in the effective treatment of PH that target the underlying mechanisms. To date, there is no FDA-approved DPI indicated for the treatment of PH. Fasudil is a novel RhoA/Rho kinase (ROCK) inhibitor that has shown great potential in effectively treating pulmonary hypertension. This systematic study is the first to report on the design and development of DPI formulations comprised of respirable nanoparticles/microparticles using particle engineering design by advanced spray drying. In addition, comprehensive physicochemical characterization, in vitro aerosol aerosol dispersion performance with different types of human DPI devices, in vitro cell-drug dose response cell viability of different human respiratory cells from distinct lung regions, and in vitro transepithelial electrical resistance (TEER) as air-interface culture (AIC) demonstrated that these innovative DPI fasudil formulations are safe on human lung cells and have high aerosol dispersion performance properties.",
keywords = "Advanced spray drying, Air-interface culture (AIC), Dry powder inhaler, In vitro TEER, In vitro human lung cells, Particle engineering design, Pulmonary hypertension, Solid-state characterization, Targeted lung delivery",
author = "Priya Muralidharan and Don Hayes and Fineman, {Jeffrey R.} and Black, {Stephen M.} and Mansour, {Heidi M.}",
note = "Funding Information: Acknowledgments: SEM images and data were collected in the W.M. Keck Center for Nano-Scale Imaging in the Department of Chemistry and Biochemistry at the University of Arizona with funding from the W.M. Keck Foundation Grant. Raman data was collected in the Imaging Cores Materials Imaging and Characterization Facility supported by the office of Research, Discovery and Innovation at The University of Arizona. This material is based upon work supported by the National Science Foundation under Grant Number #0619599 and Arizona Proposition 301: Technology and Research Initiative Fund (A.R.S.§15-1648). X-ray diffraction data was collected in the X-Ray Diffraction Facility of the Department of Chemistry and Biochemistry at The University of Arizona. The authors sincerely thank Brooke Beam-Massani, Paul Wallace and Andrei Astachkine for core facility access and assistance. The authors sincerely thank Palash Gangopadhyay (ATR-FTIR). A special thanks to Andrew King, Renishaw Inc. for obtaining Raman spectra using 785 nm laser. PM would like to thank Nelusha Malithi Fonseka and Sriram Srinivasan for their assistance in preparing the manuscript. The authors gratefully acknowledge financial support from the College of Pharmacy graduate student fellowship awarded to PM. This work was supported by NIH NHLBI R01HL137282 (HMM, SMB, and JRF), NIH NHLBI R01HL60190 (SMB), NIH NIA R21AG054766 (HMM), NIH NIAID R21AI135935 (HMM and SMB), and NIH NHLBI P01HL103453 (HMM), and NIH NHLBI P01HL134610 (SMB), and NIH NHLBI P01HL146369 (SMB and JRF). Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2021",
month = dec,
doi = "10.3390/pharmaceutics13122188",
language = "English (US)",
volume = "13",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "12",
}