巨噬细胞膜包裹的PEG-PLGA载雷公藤红素纳米粒靶向治疗重症急性胰腺炎的大鼠体内药效学研究

Celastrol-loaded macrophage membrane camouflaged PEG-PLGA nano-particles for targeted therapy of severe acute pancreatitis in rats

急性胰腺炎常伴随局部或全身性炎症反应,本研究旨在开发一种雷公藤红素靶向治疗急性胰腺炎的策略。首先,选择小鼠单核巨噬细胞RAW264.7为模型巨噬细胞,通过细胞溶胀、机械破坏和密度梯度离心法提取巨噬细胞膜;采用探头超声法制备平均粒径约150 nm左右的PEG-PLGA纳米粒;利用挤膜法将细胞膜挤过400 nm多孔聚碳酸酯膜而制备巨噬细胞膜包裹的PEG-PLGA纳米粒。体内分布研究发现,该细胞膜包裹的纳米粒有很好地胰腺炎症靶向性;与未包膜纳米粒比较,载雷公藤红素巨噬细胞膜包裹的纳米粒对胰腺局部和全身炎症有较好的治疗效果。

Severe acute pancreatitis（SAP） is characterized by both local and systemic inflammatory responses. This study was designed to develop a site-specific delivery strategy for SAP therapy using celastrol（CLT）. First, murine RAW264.7 cells were used as a model of macrophage cell line, cell membranes were obtained by emptying intracellular contents via hypotonic lysing, mechanical membrane disruption, and differential centrifugation. Poly（ethylene glycol） methyl ether-block-poly（lactic-co-glycolic acid）（PEG-PLGA） nanoparticles（NPs） were then prepared by sonication. With the collected membrane materials, macrophage membrane coated PEG-PLGA NPs（RNPs） were then prepared by extrusion through a 400 nm polycarbonate membrane. Biodistribution study in rats with SAP showed RNPs selectively accumulated in the inflamed pancreatic tissues. Compared with CLT loaded NPs, CLT loaded RNPs were proven to effectively attenuate local pancreatic inflammation and systemic inflammation in rats with SAP.