Radiolabelling of Antigen and Liposomes for Vaccine Biodistribution Studies 英文参考文献.docVIP

Pharmaceutics 2010, 2, 91–104; doi:10.3390/pharmaceutics2020091 OPEN ACCESS pharmaceutics ISSN 1999-4923 /journal/pharmaceutics Article Radiolabelling of Antigen and Liposomes for Vaccine Biodistribution Studies Malou Henriksen-Lacey, Vincent Bramwell and Yvonne Perrie * School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK * Author to whom correspondence should be addressed; E-Mail: y.perrie@aston.ac.uk; Tel.:+ 0121 204 3991. Received: 19 March 2010; in revised form: 29 March 2010 / Accepted: 30 March 2010 / Published: 31 March 2010 Abstract: A relatively simple and effective method to follow the movement of pharmaceutical preparations such as vaccines in biodistribution studies is to radiolabel the components. Whilst single radiolabelling is common practice, in vaccine systems containing adjuvants the ability to follow both the adjuvant and the antigen is favourable. To this end, we have devised a dual-radiolabelling method whereby the adjuvant (liposomes) is labelled with 3H and the antigen (a subunit protein) with 125I. This model is stable and reproducible; we have shown release of the radiolabels to be negligible over periods of up to 1 week in foetal calf serum at 37 oC. In this paper we describe the techniques which enable the radiolabelling of various components, assessing stability and processing of samples which all for their application in biodistribution studies. Furthermore we provide examples derived from our studies using this model in tuberculosis vaccine biodistribution studies. Key words: liposomes; vaccines; radiolabelling; pharmacokinetics; biodistribution 1. Introduction 1.1. The origins and applications of radioisotopes The history of using radioisotopes as tracer molecules dates back to 1913 when George De Hevesy was struggling to separate a mixture of lead and Radium D