Citation: Tong Zhang, Chao Sun, Shubin Yang, Zimin Cai, Sifeng Zhu, Wendian Liu, Yun Luan, Cheng Wang. Inhalation of taraxasterol loaded mixed micelles for the treatment of idiopathic pulmonary fibrosis[J]. Chinese Chemical Letters, ;2024, 35(8): 109248. doi: 10.1016/j.cclet.2023.109248 shu

Inhalation of taraxasterol loaded mixed micelles for the treatment of idiopathic pulmonary fibrosis

Tong Zhang ^{a, 1} ,
Chao Sun ^{b, 1} ,
Shubin Yang ^d ,
Zimin Cai ^a ,
Sifeng Zhu ^a ,
Wendian Liu ^a ,
Yun Luan ^{b, e, *,} ,
Cheng Wang ^{a, c, *,}

a.
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
b.
Central Research Laboratory, Department of General Surgery, the Second Hospital of Shandong University, Ji'nan 250033, China
c.
Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao 266237, China
d.
Orthopedics Dept.1, Rushan people's hospital, Rushan 264500, China
e.
Department of Cardiology, the Second Hospital of Shandong University, Ji'nan 250033, China

luanyun@sdu.edu.cn

cheng13980029671@163.com

Received Date: 19 May 2023
Revised Date: 14 October 2023
Accepted Date: 23 October 2023
Available Online: 2 November 2023

Figures(5)

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal lung disease characterized by pulmonary inflammation, oxidative stress, and excessive extracellular matrix (ECM) deposition. Current anti-fibrotic drugs for IPF treatment in the clinic lack selectivity and demonstrate unsatisfactory efficacy, highlighting the urgent necessity for a novel therapeutic strategy. Taraxasterol (TA), which has biological activities against lung injury induced by various factors, is a potential anti-IPF drug due to its anti-inflammatory, antioxidant and lung-protective effects. However, the protective effect of TA on IPF has not been confirmed, and its clinical application is limited due to its poor aqueous solubility. In this study, we demonstrated that TA could inhibit epithelial-mesenchymal transition (EMT) and migration of A549 cells by inhibiting the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. To improve the aqueous solubility and pulmonary administration performance of TA, we prepared TA loaded methoxy poly(ethylene glycol)-poly(d, l-lactide) (mPEG-PLA)/d-α-tocopheryl polyethylene glycol succinate (TPGS) mixed polymeric micelles (TA-PM). Then a MicroSprayer^Ⓡ Aerosolizer was used to deliver TA-PM once every two days for three weeks to evaluate their therapeutic effects on bleomycin (BLM)-induced IPF mice. Our results demonstrated that inhaled TA-PM significantly inhibited BLM-induced inflammation, oxidative stress and fibrosis in lung tissue. Furthermore, TA-PM exhibited high pulmonary deposition and retention by pulmonary administration, along with a favorable safety profile. Overall, this study emphasizes the potential of inhaled TA-PM as a promising treatment for IPF, providing a new opportunity for their clinical application.
- Taraxasterol,
- Idiopathic pulmonary fibrosis,
- Mixed polymeric micelles,
- Pulmonary administration,
- Bleomycin
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