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TLR4 激动剂对氢氧化铝凝胶沉降作用的表征:激光散射光学剖析的新应用。

Characterization of TLR4 agonist effects on alhydrogel® sedimentation: a novel application of laser scattering optical profiling.

机构信息

Infectious Disease Research Institute, Seattle, Washington 98104, USA.

出版信息

J Pharm Sci. 2012 Nov;101(11):4357-64. doi: 10.1002/jps.23307. Epub 2012 Aug 28.

DOI:10.1002/jps.23307
PMID:22927211
Abstract

Aluminum salt formulations such as Alhydrogel® have been used for decades as effective and safe vaccine adjuvants. Aluminum salts have a high adsorptive capacity for vaccine antigens and other immunomodulatory molecules such as Toll-like receptor (TLR) agonists. However, the characterization of some Alhydrogel®-adsorbed TLR agonists is challenging, requiring destructive analysis, complex instrumentation, and/or desorption method development. In this report, we characterize the effects of an Alhydrogel®-adsorbed synthetic Toll-like receptor 4 (TLR4) agonist on aluminum salt sedimentation behavior using laser scattering optical profiling. This method facilitates the detection of the effects on aluminum salt sedimentation behavior of low amounts of adsorbed TLR4 agonist (<30 μM) with a minimum of sample preparation and analysis time by collecting light transmission simultaneously from the complete vertical profile of the sample.

摘要

铝盐制剂,如 Alhydrogel®,已被广泛应用于医学领域数十年,被认为是安全有效的疫苗佐剂。铝盐具有较高的抗原吸附能力,同时还可以吸附其他免疫调节分子,如 Toll 样受体(TLR)激动剂。然而,一些 Alhydrogel®吸附的 TLR 激动剂的特性分析具有一定挑战性,需要破坏性分析、复杂的仪器设备以及(或)解吸方法的开发。在本报告中,我们采用激光散射光学剖析的方法,研究了 Alhydrogel®吸附的合成 Toll 样受体 4(TLR4)激动剂对铝盐沉淀行为的影响。这种方法可以通过从样品的完整垂直剖面同时收集透光率,在最小的样品制备和分析时间内,检测吸附的 TLR4 激动剂(<30μM)对铝盐沉淀行为的影响,检测下限低。

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