Rheumatoid arthritis, a chronic disease, affects from 0.5% to 1% of the world population. The main consequences include loss of joint functionality and severe pain, with lost in life quality and increased risk of morbidity and mortality. The main strategy for RA treatment relies in early diagnosis as targeted therapy. In this regard, the development and application of designed/engineered nanoparticles may represent an innovative approach and the key to success, since is a personalized nanodrug. Thus, we have synthetized, characterized, and in vivo evaluated a tri-loaded monoclonal antibody nanoparticle. For the production we used a mix of monoclonal antibodies: adalimumab, rituximab and trastuzumab to surround all RA metabolic pathways. The characterization included atomic force microscopy, dynamic light scattering analysis and entrapment efficacy using BCA analysis. The in vivo evaluation was done in mice. At this stage we used animals to assess the pharmacokinetics, the tissue distribution as the proof of concept (therapeutic efficacy) of the nanoparticles developed in inducted animals with rheumatoid arthritis. The interpretation of our results revealed that a spherical shaped nanoparticle has been produced with a mean size of 229.7 nm, and a polydispersity index of 0.191. This data has been corroborated by DLS and AFM analysis. The pre-clinical (in vivo) evaluation demonstrated a low elimination rate of 2,34 L/hour, with a purge of 0,42 h. The therapeutic efficacy showed that the nanoparticles have an increased therapeutic effect than the conventional drug with a reduction in all main parameters including the interleukins.

中文翻译：

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工程化的高负荷混合单克隆抗体（阿达木单抗，利妥昔单抗和曲妥珠单抗）聚合物纳米颗粒用于类风湿关节炎的治疗：概念验证。

类风湿关节炎是一种慢性疾病，影响世界人口的0.5％至1％。主要后果包括关节功能丧失和剧烈疼痛，生活质量下降，发病和死亡的风险增加。RA治疗的主要策略依赖于早期诊断作为靶向治疗。在这方面，由于是个性化的纳米药物，设计/工程化的纳米颗粒的开发和应用可能代表了一种创新的方法和成功的关键。因此，我们已经合成，表征并在体内评估了三载单克隆抗体纳米颗粒。在生产中，我们使用了单克隆抗体的混合物：阿达木单抗，利妥昔单抗和曲妥珠单抗来包围所有RA代谢途径。表征包括原子力显微镜，动态光散射分析和使用BCA分析的包封效果。在体内评价小鼠进行。在这个阶段，我们用动物来评估药物动力学，组织分布是类风湿性关节炎诱导动物体内开发的纳米颗粒的概念证明（治疗功效）。我们对结果的解释表明，已生产出球形纳米颗粒，平均粒径为229.7 nm，多分散指数为0.191。DLS和AFM分析已证实了该数据。临床前（体内评价）显示清除速度低，为2.34 L /小时，清除时间为0.42 h。治疗功效表明，纳米颗粒具有比常规药物更高的治疗效果，同时降低了包括白介素在内的所有主要参数。