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壳聚糖增强免疫纳米载体对阿尔茨海默病淀粉样蛋白脑血管沉积物的稳定性和靶向性。

Chitosan enhances the stability and targeting of immuno-nanovehicles to cerebro-vascular deposits of Alzheimer's disease amyloid protein.

机构信息

Department of Basic Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA.

出版信息

Nanomedicine. 2012 Feb;8(2):250-60. doi: 10.1016/j.nano.2011.06.008. Epub 2011 Jun 24.

Abstract

UNLABELLED

Alzheimer's disease amyloid β (Aβ) proteins accumulate in the cerebral vasculature and cause cerebral amyloid angiopathy (CAA). The objective of this study was to resolve critical formulation issues in developing nanoparticles (NPs) capable of permeating the blood brain barrier (BBB) and targeting cerebrovascular Aβ proteins. To achieve this objective we designed immuno-nanovehicles, which are chitosan-coated poly lactic-co-glycolic acid (PLGA) NPs conjugated with a novel anti-Aβ antibody. Measurements made according to Derjaguin-Landau-Verwey-Overbeek (DLVO) theory indicated that the immuno-nanovehicles have a much lower propensity to aggregate than the control nanovehicles. Immuno-nanovehicles showed enhanced uptake at the BBB and better targeting of the Aβ proteins deposited in the CAA model in vitro in comparison with the control nanovehicles. In addition, chitosan enhanced aqueous dispersibility and increased the stability of immuno-nanovehicles during lyophilization, thus transforming them into ideal vehicles for delivering therapeutic and diagnostic agents to the cerebral vasculature ridden with vascular amyloid.

FROM THE CLINICAL EDITOR

In this study, the authors report the development of chitosan-coated PLGA nanoparticles conjugated with anti-amyloid antibody to be used as immuno-nanovehicles to image cerebral amyloid angiopathy deposits in vivo. This method enables delivering therapeutic and diagnostic agents to the cerebral vasculature ridden with vascular amyloid.

摘要

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阿尔茨海默病淀粉样 β(Aβ)蛋白在脑血管中积累,导致脑淀粉样血管病(CAA)。本研究的目的是解决开发能够穿透血脑屏障(BBB)并靶向脑血管 Aβ 蛋白的纳米颗粒(NP)的关键制剂问题。为了实现这一目标,我们设计了免疫纳米载体,它是壳聚糖包覆的聚乳酸-共-羟基乙酸(PLGA)纳米颗粒与新型抗 Aβ 抗体偶联而成。根据德加古因-兰德奥韦尔贝克(DLVO)理论进行的测量表明,免疫纳米载体比对照纳米载体的聚集倾向低得多。与对照纳米载体相比,免疫纳米载体在 BBB 处的摄取增强,并且在体外 CAA 模型中对沉积的 Aβ 蛋白的靶向性更好。此外,壳聚糖提高了免疫纳米载体在冻干过程中的水分散性和稳定性,从而将其转化为向充满血管淀粉样蛋白的脑血管输送治疗和诊断剂的理想载体。

临床编辑按

在这项研究中,作者报告了壳聚糖包覆的 PLGA 纳米颗粒与抗淀粉样蛋白抗体偶联作为免疫纳米载体,用于在体内成像脑淀粉样血管病沉积物。这种方法能够将治疗和诊断剂递送至充满血管淀粉样蛋白的脑血管。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce31/3767177/f872d46567eb/nihms308235f1.jpg

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