TY - JOUR
T1 - Telmisartan Nanosuspension for Inhaled Therapy of COVID-19 Lung Disease and Other Respiratory Infections
AU - Chen, Daiqin
AU - Yun, Xin
AU - Lee, Daiheon
AU - Dicostanzo, Joseph R.
AU - Donini, Oreola
AU - Shikuma, Cecilia M.
AU - Thompson, Karen
AU - Lehrer, Axel T.
AU - Shimoda, Larissa
AU - Suk, Jung Soo
N1 - Funding Information:
This work was supported by the National Institute of Health (R01HL137716, R01HL073859, and P30EY001765) and the Cystic Fibrosis Foundation (SUK18I0). The NHP study was supported by a personal donation of J.R.D. Johns Hopkins University utilized the nonclinical and preclinical services program offered by the National Institute of Allergy and Infectious Diseases. The authors thank Drs. Sara Cherry and David C. Schultz and the University of Pennsylvania High-throughput Screening Core for supporting the in vitro anti-SARS-CoV-2 studies in Calu-3 cells. We would like to thank BIOQUAL, Inc. for conduct of the NHP study. Specifically, thanks to Deborah Weiss for veterinary care; John Misamore, Holly Thomasson, and Nick Solomotis for NHP facility management and coordination; Jake Yalley-Ogunro for sample processing and shipments, and Hanne Andersen, the BIOQUAL, Inc. PI.
Publisher Copyright:
© 2023 American Chemical Society. All rights reserved.
PY - 2023/1/2
Y1 - 2023/1/2
N2 - Vaccine hesitancy and the occurrence of elusive variants necessitate further treatment options for coronavirus disease 2019 (COVID-19). Accumulated evidence indicates that clinically used hypertensive drugs, angiotensin receptor blockers (ARBs), may benefit patients by mitigating disease severity and/or viral propagation. However, current clinical formulations administered orally pose systemic safety concerns and likely require a very high dose to achieve the desired therapeutic window in the lung. To address these limitations, we have developed a nanosuspension formulation of an ARB, entirely based on clinically approved materials, for inhaled treatment of COVID-19. We confirmed in vitro that our formulation exhibits physiological stability, inherent drug activity, and inhibitory effect against SARV-CoV-2 replication. Our formulation also demonstrates excellent lung pharmacokinetics and acceptable tolerability in rodents and/or nonhuman primates following direct administration into the lung. Thus, we are currently pursuing clinical development of our formulation for its uses in patients with COVID-19 or other respiratory infections.
AB - Vaccine hesitancy and the occurrence of elusive variants necessitate further treatment options for coronavirus disease 2019 (COVID-19). Accumulated evidence indicates that clinically used hypertensive drugs, angiotensin receptor blockers (ARBs), may benefit patients by mitigating disease severity and/or viral propagation. However, current clinical formulations administered orally pose systemic safety concerns and likely require a very high dose to achieve the desired therapeutic window in the lung. To address these limitations, we have developed a nanosuspension formulation of an ARB, entirely based on clinically approved materials, for inhaled treatment of COVID-19. We confirmed in vitro that our formulation exhibits physiological stability, inherent drug activity, and inhibitory effect against SARV-CoV-2 replication. Our formulation also demonstrates excellent lung pharmacokinetics and acceptable tolerability in rodents and/or nonhuman primates following direct administration into the lung. Thus, we are currently pursuing clinical development of our formulation for its uses in patients with COVID-19 or other respiratory infections.
KW - acute respiratory distress syndrome (ARDS)
KW - inhalational therapy
KW - nanosuspension
KW - renin-angiotensin system
KW - respiratory infection
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U2 - 10.1021/acs.molpharmaceut.2c00448
DO - 10.1021/acs.molpharmaceut.2c00448
M3 - Article
C2 - 36448927
AN - SCOPUS:85143393696
SN - 1543-8384
VL - 20
SP - 750
EP - 757
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
IS - 1
ER -