Amphiphilic Polyanhydride
Nanoparticles Stabilize <i>Bacillus anthracis</i> Protective
Antigen
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Abstract
Advancements toward an improved vaccine against <i>Bacillus
anthracis</i>, 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(<i>p</i>-carboxyphenoxy)hexane and 1,8-bis(<i>p</i>-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