Preparation and brain delivery property of biodegradable polymersomes conjugated with OX26

被引:215
|
作者
Pang, Zhiqing [1 ]
Lu, Wei [1 ]
Gao, Huile [1 ]
Hu, Kaili [1 ]
Chen, Jun [1 ]
Zhang, Chaolin [1 ]
Gao, Xiaoling [1 ]
Jiang, Xinguo [1 ]
Zhu, Cuiqing [2 ]
机构
[1] Fudan Univ, Sch Pharm, Dept Pharmaceut, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Med Sch, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
polymersomes; OX26; brain delivery; blood-brain barrier (BBB); NC-1900;
D O I
10.1016/j.jconrel.2008.03.007
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A novel drug carrier for brain delivery, poly(ethyleneglycol)-poly(epsilon-caprolactone) (PEG-PCL) polymersomes conjugated with mouse-anti-rat monoclonal antibody OX26 (OX26-PO), was developed and its brain delivery property was evaluated. The diblock copolymers of methoxy-PEG-PCL and Maleimide-PEG-PCL were synthesized and applied to prepare polymersomes (PO) which were verified by direct cryogenic temperature transmission electron micrograph (Cryo-TEM) imaging. The TEM examination and dynamic light scattering results showed that OX26-PO had a round and vesicle-like shape with a mean diameter around 100 nm. Coupling of OX26 with PO was confirmed by immuno-gold labeling of OX26 visualized under the TEM and X-ray photoelectron spectroscopy test. The surface OX26 densities were obtained from enzyme-linked immunosorbant assay. The result of brain delivery in rats proved that the increase of surface OX26 density of OX26-PO decreased blood AUC. The optimized OX26 number conjugated per polymersome was 34, which can acquire the greatest blood-brain barrier (BBB) permeability surface area product and percentage of injected dose per gram brain (%ID/g brain). Furthermore, NC-1900, as a model peptide, was encapsulated into OX26(34)-PO and improved the scopolamine-induced learning and memory impairments in a water maze task via i.v. administration. These results indicated that OX26(34)-PO is a promising carrier for peptide brain delivery. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:120 / 127
页数:8
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