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用于疫苗递送的载体红细胞的制备及体外特性研究

Preparation and in vitro characterization of carrier erythrocytes for vaccine delivery.

作者信息

Hamidi M, Zarei N, Zarrin A H, Mohammadi-Samani S

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583 Shiraz, Iran.

出版信息

Int J Pharm. 2007 Jun 29;338(1-2):70-8. doi: 10.1016/j.ijpharm.2007.01.025. Epub 2007 Jan 20.

DOI:10.1016/j.ijpharm.2007.01.025
PMID:17317049
Abstract

Erythrocytes as the most readily available and abundant cells within the body, have been studied extensively for their potential application as drug delivery carriers. In this study, human erythrocytes have been loaded by bovine serum albumin (BSA) as a model antigen/protein using hypotonic preswelling method for targeted delivery of this antigen to antigen-presenting cells (APCs). A series of in vitro tests have been carried out to characterize the carrier cells in vitro, including loading parameters, BSA and hemoglobin release kinetics, hematological indices, particle size distribution, SEM analysis, osmotic and turbulence fragility, and osmotic competency. BSA was loaded in erythrocytes with a loaded amount of 1.98+/-0.009mg with antigen release from carrier cells showing a zero-order kinetic consistent to that of the cell lysis. The apparent cell sizes, measured using laser scattering, were not significantly different from normal erythrocytes, but the real sizes, measured using SEM, and surface topologies were quite different between loaded and unloaded cells. The BSA-loaded cells were remarkably more fragile and less deformable compared to the normal cells. Totally, BSA-loaded erythrocytes seem to be a promising delivery system for reticuloendothelial system (RES) targeting of the antigens.

摘要

红细胞作为体内最容易获得且数量丰富的细胞,因其作为药物递送载体的潜在应用而受到广泛研究。在本研究中,使用低渗预膨胀法将牛血清白蛋白(BSA)作为模型抗原/蛋白质加载到人类红细胞中,以将该抗原靶向递送至抗原呈递细胞(APC)。已经进行了一系列体外试验来表征载体细胞的体外特性,包括加载参数、BSA和血红蛋白释放动力学、血液学指标、粒度分布、扫描电子显微镜(SEM)分析、渗透和湍流脆性以及渗透能力。BSA以1.98±0.009mg的加载量加载到红细胞中,载体细胞中的抗原释放呈现与细胞裂解一致的零级动力学。使用激光散射测量的表观细胞大小与正常红细胞没有显著差异,但使用SEM测量的实际大小以及加载和未加载细胞之间的表面拓扑结构有很大不同。与正常细胞相比,加载BSA的细胞明显更脆弱且变形能力更弱。总体而言,加载BSA的红细胞似乎是一种有前景的用于抗原靶向网状内皮系统(RES)的递送系统。

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