B6 Peptide-Modified PEG-PLA Nanoparticles for Enhanced Brain Delivery of Neuroprotective Peptide

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• 作者：Zhongyang Liu ; Xiaoling Gao ; Ting Kang ; Mengyin Jiang ; Deyu Miao ; Guangzhi Gu ; Quanyin Hu ; Qingxiang Song ; Lei Yao ; Yifan Tu ; Hongzhuan Chen ; Xinguo Jiang ; Jun Chen
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：June 19, 2013
• 年：2013
• 卷：24
• 期：6
• 页码：997-1007
• 全文大小：646K
• 年卷期：v.24,no.6(June 19, 2013)
• ISSN：1520-4812

文摘

The blood-brain barrier (BBB), which is formed by the brain capillary wall, greatly hinders the development of new drugs for the brain. Over the past decades, among the various receptor-mediated endogenous BBB transport systems, the strategy of using transferrin or anti-transferrin receptor antibodies to facilitate brain drug delivery system is of particular interest. However, the application of large proteins still suffers from the drawbacks including synthesis procedure, stability, and immunological response. Here, we explored a B6 peptide discovered by phase display as a substitute for transferrin, and conjugated it to PEG-PLA nanoparticles (NP) with the aim of enhancing the delivery of neuroprotective drug across the BBB for the treatment of Alzheimer鈥檚 disease. B6-modified NP (B6-NP) exhibited significantly higher accumulation in brain capillary endothelial cells via lipid raft-mediated and clathrin-mediated endocytosis. In vivo, fluorescently labeled B6-NP exhibited much higher brain accumulation when compared with NP. Administration of B6-NP encapsulated neuroprotective peptide鈥擭APVSIPQ (NAP)鈥攖o Alzheimer鈥檚 disease mouse models showed excellent amelioration in learning impairments, cholinergic disruption, and loss of hippocampal neurons even at lower dose. These findings together suggested that B6-NP might serve as a promising DDS for facilitating the brain delivery of neuropeptides.