Segura S, Gamazo C, Irache J M, Espuelas S
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, 31008 Pamplona, Spain.
Antimicrob Agents Chemother. 2007 Apr;51(4):1310-4. doi: 10.1128/AAC.00890-06. Epub 2007 Jan 12.
The aim of this study was to evaluate the activity of gamma interferon (IFN-gamma) when it was either adsorbed onto or loaded into albumin nanoparticles. Brucella abortus-infected macrophages and infected BALB/c mice were selected as the models for testing of the therapeutic potentials of these cytokine delivery systems, in view of the well-established role of IFN-gamma-activated macrophages for the control of Brucella sp. infections. Whereas the encapsulation of IFN-gamma inside the matrix of nanoparticles completely abrogated its activity, adsorbed IFN-gamma increased by 0.75 log unit the bactericidal effect induced by RAW macrophages activated with free IFN-gamma, along with a higher level of production of nitric oxide. In infected BALB/c-mice, IFN-gamma adsorbed onto nanoparticles was also more active than free cytokine in reducing the number of bacteria in the spleens, and the effect was mediated by an increased ratio of IFN-gamma-secreting (Th1) to interleukin-4-secreting (Th2) cells. Overall, albumin nanoparticles would be suitable as carriers that target IFN-gamma to macrophages and, thus, potentiate their therapeutic activity.
本研究的目的是评估γ干扰素(IFN-γ)吸附于白蛋白纳米颗粒或载入白蛋白纳米颗粒时的活性。鉴于IFN-γ激活的巨噬细胞在控制布鲁氏菌属感染方面已确立的作用,选择感染流产布鲁氏菌的巨噬细胞和感染的BALB/c小鼠作为测试这些细胞因子递送系统治疗潜力的模型。虽然纳米颗粒基质内包封的IFN-γ完全消除了其活性,但吸附的IFN-γ使游离IFN-γ激活的RAW巨噬细胞诱导的杀菌效果增加了0.75个对数单位,同时一氧化氮的产生水平更高。在感染的BALB/c小鼠中,吸附于纳米颗粒的IFN-γ在减少脾脏细菌数量方面也比游离细胞因子更具活性,且该效应由分泌IFN-γ的(Th1)细胞与分泌白细胞介素-4的(Th2)细胞的比例增加介导。总体而言,白蛋白纳米颗粒将适合作为将IFN-γ靶向巨噬细胞的载体,从而增强其治疗活性。