Encapsulation into amphiphilic polyanhydride microparticles stabilizes Yersinia pestis antigens
Encapsulation into amphiphilic polyanhydride microparticles stabilizes Yersinia pestis antigens
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DOI：
10.1016/j.actbio.2010.01.040
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发表时间：
2010-08-01
影响因子：
9.7
通讯作者：
Narasimhan, Balaji
中科院分区：
文献类型：
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作者：
Carrillo-Conde, Brenda;Schiltz, Elise;Narasimhan, Balaji
本研究的主要目标是设计基于聚酸酐的可生物降解聚合物递送系统，以改善耶尔森氏菌比索抗原的结构完整性。因此，全长 Y 比索融合蛋白 (F1-V) 或重组 Y 比索融合蛋白 (F1(B2T1)-V10) 被封装并从基于 1,6-双(对羧基苯氧基)己烷 (CPH) 和癸二酸的微粒中释放酸（SA）共聚物和1,8-双（对羧基苯氧基）-3,6-二氧辛烷（CPTEG）和通过低温雾化制备的CPH共聚物。使用酶联免疫吸附测定来测量释放的蛋白质的抗原性变化。重组F1(B2T1)-V10从疏水性CPH SA微粒释放后不稳定。但在两亲性CPTEG CPH系统中保持其结构和抗原性。全长F1-V由CPH SA和CPTEG CPH微粒稳定释放。为了确定酸酐单体对蛋白质结构的影响，在 SA 饱和溶液中孵育后，测量一级、二级和三级结构的变化，以及鼠疫耶尔森氏菌抗原的抗原性。 CPH 和 CPTEG 酸酐单体 结果表明，CPTEG 单体提供的两亲环境对于保存两种蛋白质的结构和抗原性非常重要 这些研究提供了一种方法，通过该方法可以阐明抗原不稳定性的机制，从而优化可生物降解的递送装置作为蛋白质载体和/或疫苗佐剂的体内性能 (C) 2010 Acta Materialia Inc 由 Elsevier Ltd 出版 保留所有权利
The design of biodegradable polymeric delivery systems based on polyanhydrides that would provide for improved structural integrity of Yersinia pesos antigens was the main goal of this study Accordingly, the full-length Y pesos fusion protein (F1-V) or a recombinant Y pesos fusion protein (F1(B2T1)-V10) was encapsulated and released from microparticles based on 1,6-bis(p-carboxyphenoxy)hexane (CPH) and sebacic acid (SA) copolymers and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and CPH copolymers fabricated by cryogenic atomization. An enzyme-linked immunosorbent assay was used to measure changes in the antigenicity of the released proteins The recombinant F1(B2T1)-V10 was unstable upon release from the hydrophobic CPH SA microparticles. but maintained its structure and antigenicity in the amphiphilic CPTEG CPH system The full-length F1-V was stably released by both CPH SA and CPTEG CPH microparticles. In order to determine the effect of the anhydride monomers on the protein structure, changes in the primary, secondary, and tertiary structure, as well as the antigenicity of both Y pestis antigens, were measured after incubation in the presence of saturated solutions of SA. CPH, and CPTEG anhydride monomers The results indicated that the amphiphilic environment provided by the CPTEG monomer was Important to preserve the structure and antigenicity of both proteins These studies offer an approach by which a thorough understanding of the mechanisms governing antigenic instability can be elucidated in order to optimize the in vivo performance of biodegradable delivery devices as protein carriers and/or vaccine adjuvants (C) 2010 Acta Materialia Inc Published by Elsevier Ltd All rights reserved