Inflammatory Monocyte/Macrophage Modulation by Liposome-Entrapped Spironolactone Ameliorates Acute Lung Injury in Mice

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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 Ly6Chi 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.
Funding Information
  • National Natural Science Foundation (81102088, 81170238, 81441101, 81570335)
  • Tianjin Municipal Science and Technology Committee (12JCYBJC16600, 11JCYBJC11800, 13JCYBJC22000, 15ZXJZSY00010, 15JCZDJC35000)

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