Gómez Sara, Gamazo Carlos, San Roman Beatriz, Ferrer Marta, Sanz Maria Luisa, Espuelas Socorro, Irache Juan M
Departments of Pharmaceutical Technology and Microbiology, University of Navarra, Pamplona, Spain.
Eur J Pharm Biopharm. 2008 Nov;70(3):711-7. doi: 10.1016/j.ejpb.2008.05.016. Epub 2008 Jun 6.
The adjuvant and protective capacity against anaphylactic shock of the association between rough lipopolysaccharide of Brucella ovis (LPS) coencapsulated with ovalbumin (OVA), as a model allergen, in Gantrez AN nanoparticles was investigated. Several strategies were performed in order to study the adjuvant effect of the LPS either encapsulated or coating the nanoparticles. OVA, as well as LPS, was incorporated either during the manufacturing process (OVA-encapsulated or LPS-encapsulated nanoparticles, respectively) or after the preparation (OVA-coated or LPS-coated nanoparticles, respectively). After the administration of 10 microg of OVA incorporated in the different formulations, all the nanoparticles, with or without LPS, were capable of amplifying the immune response (IgG(1) and IgG(2a)). However, in a model of sensitized mice to OVA, the formulation with OVA and LPS-entrapped inside the nanoparticles administered intradermally in three doses of 3 microg of OVA each was the only treatment that totally protected the mice from death after a challenge with an intraperitoneal injection of OVA. In contrast, the control group administered with OVA adsorbed onto a commercial alhydrogel adjuvant showed 80% mortality. These results are highly suggestive for the valuable use of Gantrez nanoparticles combined with rough LPS of B. ovis in immunotherapy.
研究了将羊布鲁氏菌粗糙脂多糖(LPS)与作为模型变应原的卵清蛋白(OVA)共包封于甘氨酸乙酯甲基丙烯酸酯共聚物(Gantrez AN)纳米颗粒中对过敏性休克的佐剂和保护能力。为了研究LPS包封或包被纳米颗粒的佐剂效应,采取了几种策略。OVA以及LPS分别在制造过程中(分别为OVA包封的或LPS包封的纳米颗粒)或制备后(分别为OVA包被的或LPS包被的纳米颗粒)加入。在给予10μg不同制剂中所含的OVA后,所有纳米颗粒,无论有无LPS,均能够增强免疫反应(IgG(1)和IgG(2a))。然而,在OVA致敏小鼠模型中,将含OVA和LPS的纳米颗粒以每剂3μg OVA皮内注射三次的方式给药,是唯一一种在腹腔注射OVA激发后能完全保护小鼠免于死亡的治疗方法。相比之下,用吸附于市售氢氧化铝佐剂上的OVA给药的对照组死亡率为80%。这些结果强烈提示甘氨酸乙酯甲基丙烯酸酯共聚物纳米颗粒与羊布鲁氏菌粗糙LPS联合用于免疫治疗具有重要价值。
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