Liquidia Technologies, Inc., Research Triangle Park, NC, USA.
Nanomedicine. 2013 May;9(4):523-31. doi: 10.1016/j.nano.2012.11.001. Epub 2012 Nov 22.
Historically it is known that presentation of vaccine antigens in particulate form, for a wide range of pathogens, has clear advantages over the presentation of soluble antigen alone [J.C. Aguilar, E.G. Rodriguez, Vaccine adjuvants revisited. Vaccine 25 (2007) 3752-3762, M. Singh, D. O'Hagan, Advances in vaccine adjuvants. Nature Biotechnology 17 (1999) 1075-1081]. Herein we describe a novel particle-based approach, which independently controls size, shape, and composition to control the delivery and presentation of vaccine antigen to the immune system. Highly uniform particles were produced using a particle molding technology called PRINT (Particle Replication in Non-wetting Templates) which is an off-shoot of imprint lithography [J Am Chem Soc 127 (2005) 10096-10100, J Am Chem Soc 126 (2004) 2322-2323, Chem Soc Rev 35 (2006) 1095-1104, J Am Chem Soc 130 (2008) 5008-5009, J Am Chem Soc 130 (2008) 5438-5439, Polymer Reviews 47 (2007) 321-327, Acc Chem Res 41 (2008) 1685-1695, Acc Chem Res 44 (10) (2011) 990-998]. Cylindrical (diameter [d]=80 nm, height [h]=320 nm) poly (lactide-co-glycolide) (PLGA) based PRINT particles were designed to electrostatically bind commercial trivalent injectable influenza vaccine. In a variety of blended PLGA formulations, these particles were safe and showed enhanced responses to influenza hemagglutinin in murine models.
Shape is one of the determining factors in interactions of nanoparticles with their biologic environment. PRINT technology is able to fabricate nearly uniform nanoparticles and this technology is tested here in murine models to effectively deliver influenza vaccine.
从历史上看,在广泛的病原体中,将疫苗抗原以颗粒形式呈现,比单独呈现可溶性抗原具有明显的优势[J.C. Aguilar,E.G. Rodriguez,Vaccine adjuvants revisited. Vaccine 25(2007)3752-3762,M. Singh,D. O'Hagan,Advances in vaccine adjuvants. Nature Biotechnology 17(1999)1075-1081]。在此,我们描述了一种新的基于颗粒的方法,该方法可独立控制大小、形状和组成,从而控制疫苗抗原递送至免疫系统并呈递。使用一种称为 PRINT(在非润湿模板中复制粒子)的颗粒成型技术可制造高度均匀的颗粒,该技术是压印光刻的分支[J. Am. Chem. Soc. 127(2005)10096-10100,J. Am. Chem. Soc. 126(2004)2322-2323,Chem. Soc. Rev. 35(2006)1095-1104,J. Am. Chem. Soc. 130(2008)5008-5009,J. Am. Chem. Soc. 130(2008)5438-5439,Polymer Reviews 47(2007)321-327,Acc. Chem. Res. 41(2008)1685-1695,Acc. Chem. Res. 44(10)(2011)990-998]。设计了直径[d]=80nm、高度[h]=320nm 的圆柱形(聚(乳酸-共-乙醇酸)(PLGA)基于 PRINT 颗粒,使其能够静电结合商业三价可注射流感疫苗。在各种混合的 PLGA 配方中,这些颗粒是安全的,并在小鼠模型中对流感血凝素表现出增强的反应。
形状是纳米颗粒与其生物环境相互作用的决定因素之一。PRINT 技术能够制造出几乎均匀的纳米颗粒,并且在此项研究中,该技术在小鼠模型中被用于有效传递流感疫苗。