Institute for Pharmaceutical Technology, Goethe-University, Frankfurt, Germany.
J Drug Target. 2011 Feb;19(2):125-32. doi: 10.3109/10611861003734001. Epub 2010 Apr 13.
Human serum albumin (HSA) nanoparticles (NP) were prepared by desolvation. Insulin or an anti-insulin receptor monoclonal antibody (29B4) were covalently coupled to the HSA NP, using the NHS-PEG-MAL-5000 crosslinker. Loperamide-loaded HSA NP with covalently bound insulin or the 29B4 antibodies induced significant antinociceptive effects in the tail-flick test in ICR (CD-1) mice after intravenous injection, demonstrating that insulin or these antibodies covalently coupled to HSA NP are able to transport loperamide across the blood-brain barrier (BBB) which it normally is unable to cross. Control loperamide-loaded HSA NP with immunoglobulin G antibodies yielded only marginal effects. The loperamide transport across the BBB using the NP with covalently attached insulin could be totally inhibited by the pretreatment with the antibody 29B4.
人血清白蛋白（HSA）纳米颗粒（NP）通过去溶剂化法制备。胰岛素或抗胰岛素受体单克隆抗体（29B4）通过 NHS-PEG-MAL-5000 交联剂共价偶联到 HSA NP 上。在尾闪烁试验中，静脉注射载有洛哌丁胺的 HSA NP 与共价结合的胰岛素或 29B4 抗体后，ICR（CD-1）小鼠表现出显著的镇痛作用，表明胰岛素或这些抗体共价偶联到 HSA NP 后能够将洛哌丁胺穿过血脑屏障（BBB），而洛哌丁胺通常无法穿过 BBB。而用免疫球蛋白 G 抗体结合的载有洛哌丁胺的 HSA NP 仅产生轻微效果。用共价附着胰岛素的 NP 进行洛哌丁胺跨 BBB 转运可以被抗体 29B4 的预处理完全抑制。
