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Article

Advanced Microparticulate/Nanoparticulate Respirable Dry Powders of a Selective RhoA/Rho Kinase (Rock) Inhibitor for Targeted Pulmonary Inhalation Aerosol Delivery

1
Department of Pharmaceutical Sciences, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, USA
2
Departments of Pediatrics and Internal Medicine, Lung and Heart-Lung Transplant Programs, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH 43205, USA
3
UCSF School of Medicine & Benioff Children’s Hospital, San Francisco, CA 94158, USA
4
Center for Translational Science, Florida International University, Port Saint Lucie, FL 34987, USA
5
The BIO5 Research Institute, The University of Arizona, Tucson, AZ 85721, USA
6
Institute of the Environment, The University of Arizona, Tucson, AZ 85721, USA
*
Author to whom correspondence should be addressed.
Academic Editors: James B. Fink and Arzu Ari
Pharmaceutics 2021, 13(12), 2188; https://doi.org/10.3390/pharmaceutics13122188
Received: 3 October 2021 / Revised: 2 December 2021 / Accepted: 3 December 2021 / Published: 17 December 2021
(This article belongs to the Special Issue Medical Aerosol Drug Delivery)
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. View Full-Text
Keywords: particle engineering design; solid-state characterization; pulmonary hypertension; targeted lung delivery; advanced spray drying; in vitro human lung cells; in vitro TEER; air-interface culture (AIC); dry powder inhaler particle engineering design; solid-state characterization; pulmonary hypertension; targeted lung delivery; advanced spray drying; in vitro human lung cells; in vitro TEER; air-interface culture (AIC); dry powder inhaler
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MDPI and ACS Style

Muralidharan, P.; Hayes, D., Jr.; Fineman, J.R.; Black, S.M.; Mansour, H.M. Advanced Microparticulate/Nanoparticulate Respirable Dry Powders of a Selective RhoA/Rho Kinase (Rock) Inhibitor for Targeted Pulmonary Inhalation Aerosol Delivery. Pharmaceutics 2021, 13, 2188. https://doi.org/10.3390/pharmaceutics13122188

AMA Style

Muralidharan P, Hayes D Jr., Fineman JR, Black SM, Mansour HM. Advanced Microparticulate/Nanoparticulate Respirable Dry Powders of a Selective RhoA/Rho Kinase (Rock) Inhibitor for Targeted Pulmonary Inhalation Aerosol Delivery. Pharmaceutics. 2021; 13(12):2188. https://doi.org/10.3390/pharmaceutics13122188

Chicago/Turabian Style

Muralidharan, Priya, Don Hayes Jr., Jeffrey R. Fineman, Stephen M. Black, and Heidi M. Mansour. 2021. "Advanced Microparticulate/Nanoparticulate Respirable Dry Powders of a Selective RhoA/Rho Kinase (Rock) Inhibitor for Targeted Pulmonary Inhalation Aerosol Delivery" Pharmaceutics 13, no. 12: 2188. https://doi.org/10.3390/pharmaceutics13122188

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