Ulbrich Karsten, Hekmatara Telli, Herbert Elisabeth, Kreuter Jörg
Institute for Pharmaceutical Technology, Goethe-University, Frankfurt, Germany.
Eur J Pharm Biopharm. 2009 Feb;71(2):251-6. doi: 10.1016/j.ejpb.2008.08.021. Epub 2008 Sep 5.
Human serum albumin (HSA) nanoparticles were manufactured by desolvation. Transferrin or transferrin receptor monoclonal antibodies (OX26 or R17217) were covalently coupled to the HSA nanoparticles using the NHS-PEG-MAL-5000 crosslinker. Loperamide was used as a model drug since it normally does not cross the blood-brain barrier (BBB) and was bound to the nanoparticles by adsorption. Loperamide-loaded HSA nanoparticles with covalently bound transferrin or the OX26 or R17217 antibodies induced significant anti-nociceptive effects in the tail-flick test in ICR (CD-1) mice after intravenous injection, demonstrating that transferrin or these antibodies covalently coupled to HSA nanoparticles are able to transport loperamide and possibly other drugs across the BBB. Control loperamide-loaded HSA nanoparticles with IgG2a antibodies yielded only marginal effects.
人血清白蛋白（HSA）纳米颗粒通过去溶剂化法制备。使用NHS-PEG-MAL-5000交联剂将转铁蛋白或转铁蛋白受体单克隆抗体（OX26或R17217）共价偶联到HSA纳米颗粒上。洛哌丁胺用作模型药物，因为它通常不能穿过血脑屏障（BBB），并通过吸附作用与纳米颗粒结合。在静脉注射后，共价结合有转铁蛋白或OX26或R17217抗体的载洛哌丁胺HSA纳米颗粒在ICR（CD-1）小鼠的甩尾试验中诱导出显著的抗伤害感受作用，表明共价偶联到HSA纳米颗粒上的转铁蛋白或这些抗体能够将洛哌丁胺以及可能的其他药物转运穿过血脑屏障。用IgG2a抗体处理的对照载洛哌丁胺HSA纳米颗粒仅产生微弱的效果。
