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

Chinese Chemical Letters 2024年第8期35卷 475-480页

作者： Tong Zhang Chao Sun Shubin Yang Zimin Cai Sifeng Zhu Wendian Liu Yun Luan Cheng Wang Key Laboratory of Marine Drugs Chinese Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Central Research Laboratory Department of General Surgerythe Second Hospital of Shandong UniversityJi’nan 250033China Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and TechnologyQingdao 266237China Orthopedics Dept.1 Rushan people’s hospitalRushan 264500China Department of Cardiology the Second Hospital of Shandong UniversityJi’nan 250033China

Idiopathic pulmonary fibrosis(IPF)is a chronic and fatal lung disease characterized by pulmonary inflam-mation,oxidative stress,and excessive extracellular matrix(ECM)*** anti-fibrotic drugs for IPF treatment in the clinic lack selectivity and demonstrate unsatisfactory efficacy,highlighting the urgent necessity for a novel therapeutic ***(TA),which has biological activities against lung injury induced by various factors,is a potential anti-IPF drug due to its anti-inflammatory,antiox-idant and lung-protective ***,the protective effect of TA on IPF has not been confirmed,and its clinical application is limited due to its poor aqueous *** 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 *** 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 mi-celles(TA-PM).Then a MicroSprayer^(R) Aerosolizer was used to deliver TA-PM once every two days for three weeks to evaluate their therapeutic effects on bleomycin(BLM)-induced IPF *** results demonstrated that inhaled TA-PM significantly inhibited BLM-induced inflammation,oxidative stress and fibrosis in lung ***,TA-PM exhibited high pulmonary deposition and retention by pul-monary administration,along with a favorable safety ***,this study emphasizes the potential of inhaled TA-PM as a promising treatment for IPF,providing a new opportunity for their clinical appli-cation.

关键词： Taraxasterol Idiopathic pulmonary fibrosis mixed polymeric micelles Pulmonary administration Bleomycin

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