Ferritin-Based Pravastatin Assembly Augments Mucus Penetration and Ameliorates Acute Lung Injury Via Rho/ROCK Signaling Pathway.

Acute lung injury (ALI) is a common respiratory disease accompanied by alveolar capillary membrane dysfunction, inflammation and alveolar fluid deposition. Currently, the primary treatment for ALI involves intravenous or oral administration of glucocorticoid drugs. However, this approach suffers from low effective drug concentrations reaching the lungs and may cause systemic toxic side effects. Therefore, there is an urgent need to develop novel therapeutic agents and optimized delivery strategies specifically tailored for ALI treatment. On one hand, pravastatin (Prv) exhibits potent anti-inflammatory and antioxidant properties and has demonstrated therapeutic efficacy in ALI treatment, positioning it as a promising drug candidate. However, its underlying mechanisms remain poorly understood. On the other hand, inhalation represents a highly promising delivery approach for ALI therapy by enhancing drug retention in the lungs. Nevertheless, this localized administration strategy still faces the challenge of mucus barrier impeding drug penetration. Herein, a ferritin-based pravastatin nanoassembly (Prv@FTn) was developed to improve the mucus-penetrating ability of Prv. In vitro and in vivo investigations revealed that Prv@FTn alleviates LPS-induced ALI symptoms through inhibition of the Rho-ROCK I/II signaling pathway. These findings suggest that mucus-penetrating Prv@FTn is a promising Rho/ROCK signaling pathway inhibitor for ALI therapy.