Formulation and characterization of poly (β amino ester) microparticles for genetic vaccine delivery
Formulation and characterization of poly (β amino ester) microparticles for genetic vaccine delivery
复制标题
DOI：
10.1016/j.jconrel.2005.04.022
复制
发表时间：
2005-10-20
影响因子：
10.8
通讯作者：
Langer, R
中科院分区：
文献类型：
--
作者：
Little, SR;Lynn, DM;Langer, R
微粒递送系统是DNA疫苗的一种有前途的和通用的增强，因为它们可以将大有效载荷的质粒和免疫调节材料靶向抗原呈递细胞（APC）。最近已经描述了pH敏感的聚-β氨基酯（PBAE），其显著增加了这种微粒制剂的澄清性和递送效率。这项工作描述了这些PBAE含有微粒的特性和配方考虑。PBAE增加质粒DNA的超螺旋含量和总体有效负载。该聚合物还显著缓冲由酯键降解产生的pH微环境，使得包封的质粒更适合于转染。质粒从微粒中的释放基于组合物中PBAE的量是可控的。转染依赖于吞噬作用，并且对于15%和25%PBAE微粒制剂是最佳的。然而，更大量的PBAE可能对细胞有毒，表明15%PBAE制剂是未来疾病特异性DNA疫苗研究中递送的合适候选物。(c)2005 Elsevier B. V.保留所有权利。
Microparticulate delivery systems are a promising and versatile enhancement to DNA vaccines because they can target large payloads of plasmid and immunomodulating materials to antigen presenting cells (APC). A pH sensitive poly-beta amino ester (PBAE) has been recently described which substantially increases adjuvancy and delivery efficiency of such microparticle formulations. This work describes the characterization and formulation considerations specific to these PBAE containing microparticles. PBAE increases the supercoiled content and overall effective loading of plasmid DNA. This polymer also significantly buffers the pH microenvironment created by ester bond degradation, rendering encapsulated plasmid more suitable for transfection. Release of plasmid from microparticles is controllable based on the amount of PBAE in the composition. Transfection is dependant upon phagocytosis, and is optimal for 15% and 25% PBAE microparticle formulations. However, larger quantities of PBAE may be toxic to cells indicating that the 15% PBAE formulation is a suitable candidate for delivery in future studies with disease specific, DNA vaccines. (c) 2005 Elsevier B.V. All rights reserved.