A dose-related positive effect of inhaled simvastatin-loaded PLGA nanoparticles on paraquat-induced pulmonary fibrosis in rats

Pulmonary fibrosis is an important complication of subacute paraquat (PQ) poisoning. Here, we reported a novel nanotherapeutic platform for PQ-induced pulmonary fibrosis in animal inhalation models using simvastatin (SV)-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs).Eight inhalations of normal saline, PQ (24 mg/kg), PQ plus SV (20 mg/kg), PQ plus SV-loaded PLGA NPs at doses of 5, 10 or 20 mg/kg or PQ plus PLGA NPs were given to rats. After the end of the treatment period, inflammatory factors and creatine phosphokinase as well as lung pathological changes and tracheal responsiveness were evaluated.Inhalation of SV-loaded PLGA NPs could significantly prevent the progression of PQ-induced pulmonary fibrosis especially at a dose of 10 mg through decreasing the serum level of inflammatory factors as well as contractile responses (p 0.001) compared to PQ group. Pathological findings also confirmed the results. However, inhalation of non-formulated SV could not prevent tissue damage and fibrosis in comparision with SV-loaded PLGA NPs.Taken together, the present work provides us an idea about the pulmonary delivery of PLGA-SV NPs using nebulizer for the treatment of PQ poisoning. However, the efficacy of this formulation in human beings and clinical use needs to be more investigated.