Amphiphilic polyanhydride nanoparticles stabilize bacillus anthracis protective antigen

L. K. Petersen, Y. Phanse, A. E. Ramer-Tait, M. J. Wannemuehler, B. Narasimhan

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)874-882
Number of pages9
JournalMolecular Pharmaceutics
Volume9
Issue number4
DOIs
StatePublished - Apr 2 2012

Fingerprint

Polyanhydrides
Nanoparticles
Antigens
Vaccines
Biological Preservation
Aluminum Hydroxide
anthrax toxin
Bacillus anthracis
Anthrax
Hydrophobic and Hydrophilic Interactions
Polymers

Keywords

  • nanoparticles
  • polyanhydrides
  • protective antigen for anthrax
  • protein stability

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Amphiphilic polyanhydride nanoparticles stabilize bacillus anthracis protective antigen. / Petersen, L. K.; Phanse, Y.; Ramer-Tait, A. E.; Wannemuehler, M. J.; Narasimhan, B.

In: Molecular Pharmaceutics, Vol. 9, No. 4, 02.04.2012, p. 874-882.

Research output: Contribution to journalArticle

Petersen, L. K. ; Phanse, Y. ; Ramer-Tait, A. E. ; Wannemuehler, M. J. ; Narasimhan, B. / Amphiphilic polyanhydride nanoparticles stabilize bacillus anthracis protective antigen. In: Molecular Pharmaceutics. 2012 ; Vol. 9, No. 4. pp. 874-882.
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