University of Natural Resources and Life Sciences, Institute for Environmental Biotechnology, Konrad Lorenz Street 20, 3430 Tulln, Austria.
Int J Pharm. 2013 Dec 15;458(1):1-8. doi: 10.1016/j.ijpharm.2013.10.022. Epub 2013 Oct 21.
The chronic autoimmune disorder rheumatoid arthritis (RA) affects millions of adults and children every year. Chronically activated macrophages secreting enzymes and inflammatory cytokines play a key role in RA. Distinctive marker molecules on the macrophage surface could be used to design a targeted drug delivery device for the treatment of RA without affecting healthy cells and tissues. Here, different methods for covalent attachment of antibodies (mAb) recognizing MHC class II molecules found on macrophages onto human serum albumin (HSA) nanocapsules were compared. HSA nanocapsules were prepared with a hydrodynamic diameter of 500.7 ± 9.4 nm and a narrow size distribution as indicated by a polydispersity index (PDI) of 0.255 ± 0.024. This was achieved by using a sonochemical process avoiding toxic cross linking agents and emulsifiers. Covalent binding of mAb on the surface of HSA nanocapsules was realized using polyethyleneglycol (PEG)3000 as spacer molecule. The presence of mAb was confirmed by confocal laser scanning microscopy (CLSM) and enzyme-linked immunosorbent assay (ELISA). Specific binding of mAb-HSA nanocapsules to MHC class II molecules on antigen-presenting cells was demonstrated by flow cytometry analysis.
慢性自身免疫性疾病类风湿关节炎（RA）每年影响着数以百万计的成年人和儿童。慢性激活的巨噬细胞分泌的酶和炎症细胞因子在 RA 中起着关键作用。巨噬细胞表面的独特标记分子可用于设计针对 RA 的靶向药物输送装置，而不会影响健康的细胞和组织。在这里，比较了将识别巨噬细胞上 MHC Ⅱ类分子的抗体（mAb）共价连接到人血清白蛋白（HSA）纳米胶囊上的不同方法。HSA 纳米胶囊通过超声化学工艺制备，具有 500.7 ± 9.4nm 的水动力学直径和 0.255 ± 0.024 的较窄粒径分布，表明多分散指数（PDI）。这是通过使用超声化学工艺避免使用有毒的交联剂和乳化剂来实现的。使用聚乙二醇（PEG）3000 作为间隔分子实现了 mAb 在 HSA 纳米胶囊表面的共价结合。通过共聚焦激光扫描显微镜（CLSM）和酶联免疫吸附试验（ELISA）证实了 mAb 的存在。通过流式细胞术分析证实了 mAb-HSA 纳米胶囊与抗原呈递细胞上 MHC Ⅱ类分子的特异性结合。
