Affiliation:
1. Institute of Functional Nano and Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon‐Based Functional Materials and Devices Soochow University Suzhou 215123 P. R. China
2. Department of medical affair Shanghai Pulmonary Hospital Tongji University School of Medicine Shanghai 200433 P. R. China
3. Department of Thoracic Surgery Shanghai Pulmonary Hospital Tongji University School of Medicine Shanghai 200433 P. R. China
Abstract
AbstractPulmonary fibrosis, a sequela of lung injury resulting from severe infection such as severe acute respiratory syndrome‐like coronavirus (SARS‐CoV‐2) infection, is a kind of life‐threatening lung disease with limited therapeutic options. Herein, inhalable liposomes encapsulating metformin, a first‐line antidiabetic drug that has been reported to effectively reverse pulmonary fibrosis by modulating multiple metabolic pathways, and nintedanib, a well‐known antifibrotic drug that has been widely used in the clinic, are developed for pulmonary fibrosis treatment. The composition of liposomes made of neutral, cationic or anionic lipids, and poly(ethylene glycol) (PEG) is optimized by evaluating their retention in the lung after inhalation. Neutral liposomes with suitable PEG shielding are found to be ideal delivery carriers for metformin and nintedanib with significantly prolonged retention in the lung. Moreover, repeated noninvasive aerosol inhalation delivery of metformin and nintedanib loaded liposomes can effectively diminish the development of fibrosis and improve pulmonary function in bleomycin‐induced pulmonary fibrosis by promoting myofibroblast deactivation and apoptosis, inhibiting transforming growth factor 1 (TGFβ1) action, suppressing collagen formation, and inducing lipogenic differentiation. Therefore, this work presents a versatile platform with promising clinical translation potential for the noninvasive inhalation delivery of drugs for respiratory disease treatment.
Funder
National Natural Science Foundation of China
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry
Cited by
2 articles.
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