Wen-Jie Ji1,2, Yong-Qiang Ma2, Xin Zhang1, Li Zhang3, Yi-Dan Zhang1, Cheng-Cheng Su1, Guo-An Xiang1, Mei-Ping Zhang3, Zhi-Chun Lin1, Lu-Qing Wei2, Peizhong P Wang4, Zhuoli Zhang1,5, Yu-Ming Li1, Xin Zhou1. 1. Tianjin Key Laboratory of Cardiovascular Remodeling & Target Organ Injury, Pingjin Hospital Heart Center, Tianjin 300162, China. 2. Department of Respiratory & Critical Care Medicine, Pingjin Hospital, Tianjin 300162, China. 3. Department of Pharmacognosy & Pharmaceutics, Logistics University of People's Armed Police Forces, Tianjin 300309, China. 4. Division of Community Health & Humanities, Faculty of Medicine, Memorial University of Newfoundland, Canada. 5. Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Abstract
AIM: To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. MATERIALS & METHODS: Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. RESULTS: Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6C(hi) monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. CONCLUSION: Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.
AIM: To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. MATERIALS & METHODS:Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. RESULTS:Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6C(hi) monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. CONCLUSION: Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.
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