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

Molecular Pharmaceutics
Eric M BachelderJean M J Fréchet

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 LC 50 of 12,500 microg/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 byproducts, which may find use in various biomedical applications including...Continue Reading

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Citations

Mar 17, 2010·Molecular Pharmaceutics·Eric M BachelderAndrea M Keane-Myers
Jan 13, 2011·Photochemistry and Photobiology·Lili YuXinJing Tang
May 14, 2011·Chemical Society Reviews·Zhen GuYi Tang
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Sep 19, 2012·Advanced Materials·Yolonda L Colson, Mark W Grinstaff
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Sep 11, 2012·Journal of the American Chemical Society·Lina CuiJean M J Fréchet
Jan 16, 2013·Chemical Communications : Chem Comm·Sandra Binauld, Martina H Stenzel
Jun 28, 2015·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Viktoriya SokolovaMatthias Epple
Jun 29, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Michael A LuzuriagaJeremiah J Gassensmith
May 5, 2020·ACS Omega·Lizbeth A Manzanares-GuevaraAlexei F Licea-Navarro

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