Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
J Drug Target. 2011 Apr;19(3):228-34. doi: 10.3109/1061186X.2010.492523. Epub 2010 Jun 14.
The blood-brain barrier is a major barrier in the neurological diseases treatment and precludes the entry of drugs from blood to brain. Here, we developed 29-amino-acid peptide derived from rabies virus glycoprotein (RVG29) peptide conjugated itraconazole-loaded albumin nanoparticles (RVG29-ITZ-NPs). The RVG29 peptide was conjugated to the albumin NPs using biotin-binding streptavidin as crosslinker. The NPs were characterized in terms of particle size, zeta potential, drug loading and release behavior in vitro. Cellular uptake of RVG29-ITZ-NPs was investigated by flow cytometry. Pharmacokinetics and brain distribution of RVG29-ITZ-NPs were investigated after intravenous administration of NPs. The particle size of RVG29-ITZ-NPs was 89.3 ± 1.9 nm as determined by dynamic light scattering. The zeta potential of RVG29-ITZ-NPs was -33.1 ± 0.9 mV. RVG29-ITZ-NPs exhibited a sustained release profile within 24 h. In vitro cellular uptake studies demonstrated that RVG29 significantly facilitated the intracellular delivery of NPs. A significant (P < 0.05) accumulation of ITZ in brain was observed for RVG29-ITZ-NPs as compared with ITZ-NPs and cyclodextrin formulation of ITZ (ITZ-CD). These results suggested that RVG29-ITZ-NPs can be exploited as a potential therapeutic formulation for the intracranial fungal infection.
血脑屏障是神经疾病治疗的主要障碍，阻止药物从血液进入大脑。在这里，我们开发了一种源自狂犬病病毒糖蛋白（RVG29）肽的 29 个氨基酸肽，将其与负载伊曲康唑的白蛋白纳米颗粒（RVG29-ITZ-NPs）结合。RVG29 肽通过生物素结合链霉亲和素作为交联剂与白蛋白 NPs 结合。NP 以粒径、Zeta 电位、体外药物载药量和释放行为进行了表征。通过流式细胞术研究了 RVG29-ITZ-NPs 的细胞摄取。静脉注射 NP 后研究了 RVG29-ITZ-NPs 的药代动力学和脑分布。动态光散射法测定 RVG29-ITZ-NPs 的粒径为 89.3±1.9nm。RVG29-ITZ-NPs 的 Zeta 电位为-33.1±0.9mV。RVG29-ITZ-NPs 在 24 小时内表现出持续释放的特征。体外细胞摄取研究表明，RVG29 显著促进了 NP 的细胞内传递。与 ITZ-NPs 和 ITZ 的环糊精制剂（ITZ-CD）相比，RVG29-ITZ-NPs 观察到 ITZ 在大脑中的显著（P<0.05）积累。这些结果表明，RVG29-ITZ-NPs 可作为颅内真菌感染的潜在治疗制剂。
