[Frontiers in Bioscience S2, 876-890, June 1, 2010]

Poly(anhydride) nanoparticles as adjuvants for mucosal vaccination

Juan M. Irache1, Hesham H. Salman1, Sara Gomez1, Socorro Espuelas1, Carlos Gamazo2

1Department of Pharmaceutics and Pharmaceutical Technology, University of Navarra, 31008, Pamplona, Spain, 2 Department of Microbiology, University of Navarra, 31008-Pamplona, Spain

TABLE OF CONTENTS

1. Abstract
2. Introduction
2. Introduction
2.1. Adjuvants
2.1.1. Depot effect
2.1.2. Effect on APCs
2.1.3. Non-specific immunostimulating effect
2.2. Polymer nanoparticles as mucosal adjuvants
2.3. Biomimetic nanoparticles
3. Poly(anhydride) nanoparticles
3.1. Preparation and characterization of poly(anhydride) nanoparticles
3.2. Bioadhesive properties of poly(anhydride) nanoparticles
3.3. Immune response
4. Perspectives
Acknowledgements
References

1. ABSTRACT

In the last years, many efforts have been directed toward the enhancement of vaccine delivery by using polymeric nanoparticles as adjuvants for mucosal immunization. However, conventional nanoparticles usually display a low capability to target specific sites within the gut and, thus, the elicited immune responses are not as high as necessary to offer the adequate protection to the host. To overcome these drawbacks, one possible strategy can be the association of nanoparticles with compounds involved in the colonization process of microorganisms. In this biomimetic context, two different examples are shown. In both cases, poly(anhydride) nanoparticles were coated with either flagellin from Salmonella Enteritidis or mannosamine. When administered by the oral route both types of ligand-coated nanoparticles induced stronger and more balanced serum titers of IgG2a and IgG1 than control nanoparticles which induced a typical Th2 response. This Th1 response enhancement may be related to the high tropism of both flagellin- and mannosylated-nanoparticles to the ileum and uptake by Peyer's patches rich in antigen presenting cells.