摘要：Idiopathic pulmonary fibrosis(IPF) is a progressive, fatal lung disease with poor survival. The advances made in deciphering IPF have led to the approval of different anti-fibrotic molecules, such as pirfenidone and nintedanib. An increasing number of studies with particles(liposomes, nanoparticles, microspheres, nanopolymersomes and nanoliposomes) modified with different functional groups have demonstrated improvement in lung targeted drug delivery. In the present study, we prepared, characterized, and evaluated spermidine(SPD) modified poly-lactic-co-glycolide nanoparticles(SPD-AKF-PLGA/NPs) as carriers for fluorofenidone(AKF) in order to improve the anti-fibrotic efficacy of this drug in lung. SPD-AKF-PLGA/NPs were prepared and functionalized by modified solvent evaporation method with spermidine(SPD), poly-lactic-co-glycolide-polyethylene glycol(PEG-PLGA) groups. The size of SPD-AKF-PLGA/NPs was 172.5±4.3 nm. The AKF release from nanoparticles was shown to be fit Higuchi model. The A549 cellular uptake of the SPD-Cou-6-NPs group was found to be almost 2-fold higher than that of the Cou-6-NPs group. Free SPD and DFMO were pre-incubated in A549 cells to further prove that the uptake of SPD-Cou-6-PLGA/NPs via PTS. As a result, the uptake of SPD-Cou-6-PLGA/NPs significantly decreased with the increase of SPD concentrations in incubation. At the higher SPD concentrations in 50 and 500 μM, the uptake of SPD-Cou-6-PLGA/NPs reduced 0.34 and 0.49-fold than that without SPD pretreatment. After pretreatment with DFMO for 36 h, the cellular uptake of SPD-Cou-6-NPs reached 1.26-fold compared to untreated DFMO group. In biodistribution study, the drug targeting index of SPD-AKF-PLGA/NPs in lung was 3.62 and 4.66-fold than that of AKF-PLGA/NPs and AKF solution, respectively. It was suggested that the SPD-AKF-PLGA/NPs could accumulate effectively in the lung. The lung histopathology changes and collagen deposition were observed by HE staining and Masson staining in efficacy study. In SPD-AKF-PLGA/NPs group, the damage was
注：因版权方要求，不能公开全文，如需全文，请咨询杂志社
