Cell-Penetrating Peptide-Modified Block Copolymer Micelles Promote Direct Brain Delivery via Intranasal Administration
Cell-Penetrating Peptide-Modified Block Copolymer Micelles Promote Direct Brain Delivery via Intranasal Administration
复制标题
DOI：
10.1007/s11095-011-0440-7
复制
发表时间：
2011-09-01
影响因子：
3.7
通讯作者：
Okada, Hiroaki
中科院分区：
文献类型：
--
作者：
Kanazawa, Takanori;Taki, Hiroyuki;Okada, Hiroaki
为了开发无创、有效的鼻-脑给药系统，我们合成了达特类似物通过酯键修饰的甲氧基聚乙二醇（MPEG）/聚己内酯（PCL）两亲性嵌段共聚物，并以香豆素为模型化合物，研究了MPEG-PCL经静脉或鼻腔给药后的脑内分布。此外，测定了用负载香豆素的MPEG-PCL或MPEG-PCL-达特转染的大鼠胶质瘤细胞对香豆素的细胞摄取。最后，我们测定了香豆素MPEG-PCL-达特鼻腔给药后的脑组织分布和生物分布，鼻腔给药后香豆素在脑组织中的含量显著高于静脉给药后。此外，使用MPEG-PCL的香豆素的细胞摄取最低，而使用Tat修饰的MPEG-PCL（MPEG-PCL-达特）的香豆素的细胞摄取高于MPEG-PCL。因此，使用MPEG-PCL-达特给药的香豆素的脑分布显著大于使用MPEG-PCL给药的香豆素的脑分布。然后，MPEG-PCL-达特给药后香豆素在非靶组织（肺、肝、心、肾和脾）中的分布低于没有纳米胶束的香豆素给药后的分布。我们已经证明，利用达特修饰的纳米胶束可以促进直接鼻内脑递送。
In order to develop non-invasive and effective nose-to-brain delivery of drugs, we synthesized Tat analog-modified methoxy poly(ethylene glycol) (MPEG)/poly(epsilon-caprolactone) (PCL) amphiphilic block copolymers through the ester bond.We evaluated the brain distribution of coumarin, acting as a model chemical, after intravenous or intranasal administration of MPEG-PCL. In addition, cellular uptake of coumarin by rat glioma cells transfected with coumarin-loaded MPEG-PCL or MPEG-PCL-Tat was determined. Finally, we determined the brain distribution and biodistribution after intranasal administration of coumarin-loaded MPEG-PCL-Tat.The amount of coumarin in the brain after intranasal administration was significantly higher than that after intravenous administration. In addition, cellular uptake of coumarin using MPEG-PCL was the lowest, while cellular uptake of coumarin using Tat-modified MPEG-PCL (MPEG-PCL-Tat) was higher than that of MPEG-PCL. Therefore, the brain distribution of coumarin administered using MPEG-PCL-Tat was significantly greater than that using MPEG-PCL. Then, the coumarin distribution after MPEG-PCL-Tat administration in non-targeted tissues (lung, liver, heart, kidney and spleen) was lower than that after coumarin administration without nanomicelles.We have demonstrated that utilization of nano-sized micelles modified with Tat can facilitate direct intranasal brain delivery.