Poly (lactide-co-glycolide)-Polymethacrylate Nanoparticles for Intramuscular Delivery of Plasmid Encoding Interleukin-10 to Prevent Autoimmune Diabetes in Mice
Poly (lactide-co-glycolide)-Polymethacrylate Nanoparticles for Intramuscular Delivery of Plasmid Encoding Interleukin-10 to Prevent Autoimmune Diabetes in Mice
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DOI：
10.1007/s11095-008-9710-4
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发表时间：
2009-01-01
影响因子：
3.7
通讯作者：
Singh, Jagdish
中科院分区：
文献类型：
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作者：
Basarkar, Ashwin;Singh, Jagdish
测定通过共混聚（丙交酯-共-乙交酯; PLGA）和甲基丙烯酸酯共聚物（EudragitA（R）E100）制备的阳离子纳米颗粒在体外和体内递送编码小鼠白细胞介素-10的治疗性基因的效率。观察血糖、血清γ-干扰素水平和胰腺组织学变化以确定疗效。注射部位骨骼肌组织学检查评价纳米粒的生物相容性，共聚焦显微镜和缓冲能力显示PLGA/E100纳米粒具有内体逃逸现象。与PLGA纳米颗粒相比，用负载质粒的PLGA/E100纳米颗粒转染HEK 293细胞导致显著（p < 0.05）更高的白细胞介素-10表达。与仅用白细胞介素-10质粒或PLGA纳米颗粒治疗的小鼠相比，用PLGA/E100纳米颗粒治疗的小鼠显示出更高的血清白细胞介素-10水平和更低的血糖水平。白细胞介素-10的高表达促进了干扰素-γ水平的抑制和胰岛浸润的减少。肌肉组织学显示纳米粒具有良好的生物相容性，不会引起慢性炎症反应，将PLGA与甲基丙烯酸酯混合制备的纳米粒可以有效安全地递送编码小鼠白细胞介素-10的质粒DNA，从而预防自身免疫性糖尿病。
Determine the efficiency of cationic nanoparticles prepared by blending poly (lactide-co-glycolide; PLGA) and methacrylate copolymer (EudragitA (R) E100) to deliver a therapeutic gene encoding mouse interleukin-10, in vitro and in vivo.Nanoparticles prepared with PLGA and E100 were evaluated for delivery of plasmid DNA encoding mouse interleukin-10 in vitro and in vivo in mice upon intramuscular injection. Blood-glucose, serum interferon-gamma levels and histology of pancreas were studied to determine therapeutic efficacy. Histological evaluation of skeletal muscle from the injection site was performed to assess the biocompatibility of nanoparticles.PLGA/E100 nanoparticles showed endosomal escape evidenced by confocal microscopy and buffering ability. Transfecting HEK293 cells with plasmid-loaded PLGA/E100 nanoparticles resulted in significantly (p < 0.05) greater expression of interleukin-10 compared to PLGA nanoparticles. Mice treated with PLGA/E100 nanoparticles displayed higher serum levels of interleukin-10 and lower blood glucose levels compared to those treated with interleukin-10 plasmid alone or PLGA nanoparticles. High expression of interleukin-10 facilitated suppression of interferon-gamma levels and reduced islet infiltration. Histology of muscle showed that nanoparticles were biocompatible and did not cause chronic inflammatory response.Nanoparticles prepared by blending PLGA with methacrylate can efficiently and safely deliver plasmid DNA encoding mouse interleukin-10 leading to prevention of autoimmune diabetes.