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Antioxidants
Volume 10
Issue 3
10.3390/antiox10030427
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Article

Design and Comprehensive Characterization of Tetramethylpyrazine (TMP) for Targeted Lung Delivery as Inhalation Aerosols in Pulmonary Hypertension (PH): In Vitro Human Lung Cell Culture and In Vivo Efficacy

by
Priya Muralidharan
1,
Maria F. Acosta
1,
Alexan I. Gomez
1,2,3,
Carissa Grijalva
1,
Haiyang Tang
3,
Jason X.-J. Yuan
3,4 and
Heidi M. Mansour
1,3,5,6,*
1
College of Pharmacy, The University of Arizona, Tucson, AZ 85721, USA
2
Department of Biomedical Engineering, The Arizona State University, Phoenix, AZ 85287, USA
3
Department of Medicine, Division of Translational & Regenerative Medicine, College of Medicine, The University of Arizona, Tucson, AZ 85721, USA
4
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, 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: Trent E. Tipple and Peter Vitiello
Antioxidants 2021, 10(3), 427; https://doi.org/10.3390/antiox10030427
Received: 7 February 2021 / Revised: 3 March 2021 / Accepted: 5 March 2021 / Published: 11 March 2021
(This article belongs to the Special Issue Antioxidants and Lung Diseases)
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Abstract

This is the first study reporting on the design and development innovative inhaled formulations of the novel natural product antioxidant therapeutic, tetramethylpyrazine (TMP), also known as ligustrazine. TMP is obtained from Chinese herbs belonging to the class of Ligusticum. It is known to have antioxidant properties. It can act as a Nrf2/ARE activator and a Rho/ROCK inhibitor. The present study reports for the first time on the comprehensive characterization of raw TMP (non-spray dried) and spray dried TMP in a systematic manner using thermal analysis, electron microscopy, optical microscopy, and Raman spectroscopy. The in vitro aerosol dispersion performance of spray dried TMP was tested using three different FDA-approved unit-dose capsule-based human dry powder inhaler devices. In vitro human cellular studies were conducted on pulmonary cells from different regions of the human lung to examine the biocompatibility and non-cytotoxicity of TMP. Furthermore, the efficacy of inhaled TMP as both liquid and dry powder inhalation aerosols was tested in vivo using the monocrotaline (MCT)-induced PH rat model. View Full-Text
Keywords: respiratory drug delivery; ligustrazine; Rho/ROCK inhibitor; antioxidant; Nrf2; lung vascular disease; advanced spray drying; monocrotaline (MCT); rat model respiratory drug delivery; ligustrazine; Rho/ROCK inhibitor; antioxidant; Nrf2; lung vascular disease; advanced spray drying; monocrotaline (MCT); rat model
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MDPI and ACS Style

Muralidharan, P.; Acosta, M.F.; Gomez, A.I.; Grijalva, C.; Tang, H.; Yuan, J.X.-J.; Mansour, H.M. Design and Comprehensive Characterization of Tetramethylpyrazine (TMP) for Targeted Lung Delivery as Inhalation Aerosols in Pulmonary Hypertension (PH): In Vitro Human Lung Cell Culture and In Vivo Efficacy. Antioxidants 2021, 10, 427. https://doi.org/10.3390/antiox10030427

AMA Style

Muralidharan P, Acosta MF, Gomez AI, Grijalva C, Tang H, Yuan JX-J, Mansour HM. Design and Comprehensive Characterization of Tetramethylpyrazine (TMP) for Targeted Lung Delivery as Inhalation Aerosols in Pulmonary Hypertension (PH): In Vitro Human Lung Cell Culture and In Vivo Efficacy. Antioxidants. 2021; 10(3):427. https://doi.org/10.3390/antiox10030427

Chicago/Turabian Style

Muralidharan, Priya, Maria F. Acosta, Alexan I. Gomez, Carissa Grijalva, Haiyang Tang, Jason X.-J. Yuan, and Heidi M. Mansour. 2021. "Design and Comprehensive Characterization of Tetramethylpyrazine (TMP) for Targeted Lung Delivery as Inhalation Aerosols in Pulmonary Hypertension (PH): In Vitro Human Lung Cell Culture and In Vivo Efficacy" Antioxidants 10, no. 3: 427. https://doi.org/10.3390/antiox10030427

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