Development and Brain Delivery of Chitosan-PEG Nanoparticles Functionalized with the Monoclonal Antibody OX26
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- 作者：Ye
- 刊名：Bioconjugate Chemistry
- 出版年：2005
- 出版时间：November 2005
- 年：2005
- 卷：16
- 期：6
- 页码：1503 - 1511
- 全文大小：585K
- 年卷期：v.16,no.6(November 2005)
- ISSN：1520-4812
文摘
The inhibition of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebralischemia. The peptide Z-DEVD-FMK is a specific caspase inhibitor, which significantly reducesvulnerability to the neuronal cell death. However, this molecule is unable to cross the blood-brainbarrier (BBB) and to diffuse into the brain tissue. Thus, the development of an effective deliverysystem is needed to provide sufficient drug concentration into the brain to prevent cell death. Usingthe avidin (SA)-biotin (BIO) technology, we describe here the design of chitosan (CS) nanospheresconjugated with poly(ethylene glycol) (PEG) bearing the OX26 monoclonal antibody whose affinityfor the transferrin receptor (TfR) may trigger receptor-mediated transport across the BBB. Thesefunctionalized CS-PEG-BIO-SA/OX26 nanoparticles (NPs) were characterized for their particle size,zeta potential, drug loading capacity, and release properties. Fluorescently labeled CS-PEG-BIO-SA/OX26 nanoparticles were administered systemically to mice in order to evaluate their efficacy forbrain translocation. The results showed that an important amount of nanoparticles were located inthe brain, outside of the intravascular compartment. These findings, which were also confirmed byelectron microscopic examination of the brain tissue indicate that this novel targeted nanoparticulatedrug delivery system was able to translocate into the brain tissue after iv administration. Consequently,these novel nanoparticles are promising carriers for the transport of the anticaspase peptide Z-DEVD-FMK into the brain.