Acid-degradable polyurethane particles for protein-based vaccines: Biological evaluation and in vitro analysis of particle degradation products

Eric M. Bachelder, Tristan T. Beaudette, Kyle E. Broaders, Sergey E. Paramonov, Jesse Dashe, Jean Frechet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Acid-degradable particles containing a model protein antigen, ovalbumin, were prepared from a polyurethane with acetal moieties embedded throughout the polymer, and characterized by dynamic light scattering and transmission electron microscopy. The small molecule degradation byproduct of the particles was synthesized and tested in vitro for toxicity indicating an LC50 of 12,500 μg/mL. A new liquid chromatography-mass spectrometry technique was developed to monitor the in vitro degradation of these particles. The degradation byproduct inside RAW macrophages was at its highest level after 24 h of culture and was efficiently exocytosed until it was no longer detectable after 4 days. When tested in vitro, these particles induced a substantial increase in the presentation of the immunodominant ovalbumin-derived peptide SIINFEKL in both macrophages and dendritic cells. In addition, vaccination with these particles generated a cytotoxic T-lymphocyte response that was superior to both free ovalbumin and particles made from an analogous but slower-degrading acid-labile polyurethane polymer. Overall, we present a fully degradable polymer system with nontoxic by products, which may find use in various biomedical applications including protein-based vaccines.

Original languageEnglish (US)
Pages (from-to)876-884
Number of pages9
JournalMolecular Pharmaceutics
Volume5
Issue number5
DOIs
StatePublished - Sep 1 2008

Keywords

  • Acid-degradable materials
  • CTL
  • LC - MS
  • Microparticles
  • Polyacetal
  • Vaccination

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this