Amphiphilic polyanhydride nanoparticles stabilize Bacillus anthracis protective antigen.

Abstract

Advancements toward an improved vaccine against Bacillus anthracis, the causative agent of anthrax, have focused on formulations composed of the protective antigen (PA) adsorbed to aluminum hydroxide. However, due to the labile nature of PA, antigen stability is a primary concern for vaccine development. Thus, there is a need for a delivery system capable of preserving the immunogenicity of PA through all the steps of vaccine fabrication, storage, and administration. In this work, we demonstrate that biodegradable amphiphilic polyanhydride nanoparticles, which have previously been shown to provide controlled antigen delivery, antigen stability, immune modulation, and protection in a single dose against a pathogenic challenge, can stabilize and release functional PA. These nanoparticles demonstrated polymer hydrophobicity-dependent preservation of the biological function of PA upon encapsulation, storage (over extended times and elevated temperatures), and release. Specifically, fabrication of amphiphilic polyanhydride nanoparticles composed of 1,6-bis(p-carboxyphenoxy)hexane and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane best preserved PA functionality. These studies demonstrate the versatility and superiority of amphiphilic nanoparticles as vaccine delivery vehicles suitable for long-term storage.

• Authors: L K Petersen, Y Phanse, A E Ramer-Tait, M J Wannemuehler, B Narasimhan
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 9 Issue 4 Pg. 874-82 (Apr 02 2012) ISSN: 1543-8392 [Electronic] United States
• PMID: 22380593 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antigens, Bacterial
• Polyanhydrides

Topics

• Antigens, Bacterial (chemistry)
• Bacillus anthracis (immunology)
• Nanoparticles (chemistry)
• Polyanhydrides (chemistry)
• Protein Stability