Journal
ANTIOXIDANTS
Volume 10, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/antiox10030427
Keywords
respiratory drug delivery; ligustrazine; Rho; ROCK inhibitor; antioxidant; Nrf2; lung vascular disease; advanced spray drying; monocrotaline (MCT); rat model
Funding
- NIH NHLBI [1R01HL137282]
- NIH NIA [R21AG054766]
- CONACyT
- National Science Foundation [0619599]
- Arizona Proposition 301: Technology and Research Initiative Fund [A.R.S. 15-1648]
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [0619599] Funding Source: National Science Foundation
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This study presents the design and development of inhaled formulations of tetramethylpyrazine (TMP), a natural product antioxidant, along with comprehensive characterization and in vitro and in vivo studies to evaluate its therapeutic potential and biocompatibility. The results suggest promising efficacy of inhaled TMP in treating pulmonary hypertension.
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.
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