title: Effect of Chitosan Properties on Immunoreactivity.
abstract: Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering and vaccine development. However, the immune response to chitosan is not clearly understood due to contradicting results in literature regarding its immunoreactivity. Thus, in this study, we analyzed effects of various biochemical properties, namely degree of deacetylation (DDA), viscosity/polymer length and endotoxin levels, on immune responses by antigen presenting cells (APCs). Chitosan solutions from various sources were treated with mouse and human APCs (macrophages and/or dendritic cells) and the amount of tumor necrosis factor-α (TNF-α) released by the cells was used as an indicator of immunoreactivity. Our results indicate that only endotoxin content and not DDA or viscosity influenced chitosan-induced immune responses. Our data also indicate that low endotoxin chitosan (<0.01 EU/mg) ranging from 20 to 600 cP and 80% to 97% DDA is essentially inert. This study emphasizes the need for more complete characterization and purification of chitosan in preclinical studies in order for this valuable biomaterial to achieve widespread clinical application.
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR 72701, USA. ravindra@uark.edu.
authors.forename: Sruthi
authors.initials: S
authors.lastname: Ravindranathan
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR 72701, USA. bkoppolu@uark.edu.
authors.forename: Bhanu Prasanth
authors.initials: BP
authors.lastname: Koppolu
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR 72701, USA. sgs004@uark.edu.
authors.forename: Sean G
authors.initials: SG
authors.lastname: Smith
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR 72701, USA. zaharoff@uark.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Zaharoff
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry* / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014783:Viscosity
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; D048271:Chitosan
keywords: chitosan; endotoxin; immune response; immunoreactivity