Fluorofenidone-loaded PLGA microspheres for targeted treatment of paraquat-induced acute lung injury in rats

Lung-targeting fluorofenidone (AKF) loaded PLGA microspheres (AKF-MS) for the treatment of paraquat (PQ)-induced acute lung injury in rats, were constructed by a solvent evaporation method. The microspheres' morphology, size distribution, drug loading ratio, encapsulation efficiency, in vitro release characteristics and tissue distributions in rats were systematically studied. Scanning electron microscopy shows the microspheres are spherical and well dispersed. The average particle size is 18.1 μm with 90% of the microspheres being in the range of 7 to 30 μm. The encapsulation efficiency (EE%) and drug loading ratio (DL%) are 80.2 ± 2.5% and 8.2 ± 1.9%, respectively. The in vitro drug release behavior of AKF-MS follows the Korsmeyer–Peppas model: Q = 11.141t0.292 (R2 = 0.9797). The tissue distribution shows that the drug concentration in lung tissue for the AKF-MS/18.1 μm suspension is significantly higher than that for the AKF solution and AKF-MS/3.9 μm, and the drug-targeting index for lung is 6.4 and 4.6-fold higher than that of AKF solution and AKF-MS/3.9 μm, respectively. In addition, AKF-MS/18.1 μm significantly reduced the circulating levels of TNF-α and IL-1β. Histopathological studies confirm that the AKF-MS treatment significantly reduced edema and neutrophil infiltration, as well as the lung interval damage. Taken together, the results of the present study demonstrate that AKF-MS/18.1 μm improved the treatment efficacy of AKF against PQ-induced acute lung injury, compared to other forms of AKF (AKF solution and AKF-MS/3.9 μm).