Kanazawa Takanori, Kaneko Mami, Niide Takaki, Akiyama Fuminari, Kakizaki Shino, Ibaraki Hisako, Shiraishi Shunsuke, Takashima Yuuki, Suzuki Toyofumi, Seta Yasuo
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan; School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi, Chiba 274-8555, Japan.
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Int J Pharm. 2017 Sep 15;530(1-2):195-200. doi: 10.1016/j.ijpharm.2017.07.077. Epub 2017 Jul 27.
Recently, nose-to-brain delivery is a highly versatile route, which, in combination with novel drugs being developed for treating intractable CNS diseases, is a promising approach for the treatment of disorders. Furthermore, nano-sized drug carriers may improve nose-to-brain drug delivery by their capability to increase the transmucosal penetration of the drugs across nasal mucosal tissue barrier. However, there is still not enough information regarding mechanism of absorption pathway from nasal cavity to brain using nanocarriers. In this study, to investigate the nose-to-brain transport pathway using nanocarriers, the distribution in whole brain, nasal mucosa, and trigeminal nerve after intranasal administration of two kinds of nanocarriers which have hydrophobic or hydrophilic moiety. We used CHHRRRRHHC peptide (CH2R4H2C) as basic peptide carriers, and modified with stearic acid (STR) as a hydrophobic moiety (STR-CH2R4H2C) or polyethylene glycol (PEG)-based block copolymer (PEG-PCL) as hydrophilic moiety (PEG-PCL-CH2R4H2C). The nose-to-brain drug delivery can be improved by using STR-CH2R4H2C and PEG-PCL-CH2R4H2C as carriers. Specifically, hydrophobic STR-CH2R4H2C is more suitable for the transport of drugs targeting the forebrain, while PEG-PCL-modified CH2R4H2C is more suitable for transporting drugs targeting the hindbrain or whole brain tissue. In conclusion, the results of this study support the possibility that drug delivery pathways can be controlled depending on the properties of different carrier complexes.
近年来，鼻-脑给药是一种极具通用性的途径，与正在研发的用于治疗难治性中枢神经系统疾病的新型药物相结合，是一种很有前景的疾病治疗方法。此外，纳米级药物载体可通过增强药物跨鼻黏膜组织屏障的黏膜穿透能力来改善鼻-脑给药。然而，关于使用纳米载体从鼻腔到脑的吸收途径机制，仍缺乏足够的信息。在本研究中，为了探究使用纳米载体的鼻-脑转运途径，我们在鼻内给予两种分别具有疏水或亲水部分的纳米载体后，观察其在全脑、鼻黏膜和三叉神经中的分布情况。我们使用CHHRRRRHHC肽（CH2R4H2C）作为基础肽载体，并用硬脂酸（STR）作为疏水部分进行修饰（STR-CH2R4H2C），或用聚乙二醇（PEG）基嵌段共聚物（PEG-PCL）作为亲水部分进行修饰（PEG-PCL-CH2R4H2C）。使用STR-CH2R4H2C和PEG-PCL-CH2R4H2C作为载体可改善鼻-脑给药。具体而言，疏水的STR-CH2R4H2C更适合于转运靶向大脑前叶的药物，而PEG-PCL修饰的CH2R4H2C更适合于转运靶向大脑后叶或全脑组织的药物。总之，本研究结果支持了根据不同载体复合物的性质来控制药物递送途径的可能性。
