title: Acid-degradable polyurethane particles for protein-based vaccines: biological evaluation and in vitro analysis of particle degradation products.
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 protein-based vaccines.
authors: Department of Chemistry, University of California, Berkeley, CA 94720-1460, USA.
authors: Eric M
authors: EM
authors: Bachelder
authors: Tristan T
authors: TT
authors: Beaudette
authors: Kyle E
authors: KE
authors: Broaders
authors: Sergey E
authors: SE
authors: Paramonov
authors: Jesse
authors: J
authors: Dashe
authors: Jean M J
authors: JM
authors: Fréchet
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002478:Cells, Cultured; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D016056:Immunodominant Epitopes / Q000276:immunology; D008027:Light; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010316:Particle Size; D011140:Polyurethanes / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D011506:Proteins / Q000737:chemistry* / Q000276:immunology; D012542:Scattering, Radiation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology
chemical_list: D000143:Acids; D004337:Drug Carriers; D016056:Immunodominant Epitopes; D011140:Polyurethanes; D011506:Proteins; D014612:Vaccines; D010047:Ovalbumin