title: Immunotoxicity and genotoxicity testing of PLGA-PEO nanoparticles in human blood cell model.
abstract: A human blood cell model for immunotoxicity and genotoxicity testing was used to measure the response to polylactic-co-glycolic acid (PLGA-PEO) nanoparticle (NP) (0.12, 3, 15 and 75 μg/cm(2) exposure in fresh peripheral whole blood cultures/isolated peripheral blood mononuclear cell cultures from human volunteers (n = 9-13). PLGA-PEO NPs were not toxic up to dose 3 μg/cm(2); dose of 75 μg/cm(2) displays significant decrease in [(3)H]-thymidine incorporation into DNA of proliferating cells after 4 h (70% of control) and 48 h (84%) exposure to NPs. In non-cytotoxic concentrations, in vitro assessment of the immunotoxic effects displayed moderate but significant suppression of proliferative activity of T-lymphocytes and T-dependent B-cell response in cultures stimulated with PWM > CON A, and no changes in PHA cultures. Decrease in proliferative function was the most significant in T-cells stimulated with CD3 antigen (up to 84%). Cytotoxicity of natural killer cells was suppressed moderately (92%) but significantly in middle-dosed cultures (4 h exposure). On the other hand, in low PLGA-PEO NPs dosed cultures, significant stimulation of phagocytic activity of granulocytes (119%) > monocytes (117%) and respiratory burst of phagocytes (122%) was recorded. Genotoxicity assessment revealed no increase in the number of micronucleated binucleated cells and no induction of SBs or oxidised DNA bases in PLGA-PEO-treated cells. To conclude on immuno- and genotoxicity of PLGA-PEO NPs, more experiments with various particle size, charge and composition need to be done.
authors.affiliation: Department of Immunology and Immunotoxicology and Department of Experimental and Applied Genetics, Slovak Medical University , Bratislava , Slovakia .
authors.forename: Jana
authors.initials: J
authors.lastname: Tulinska
authors.forename: Alena
authors.initials: A
authors.lastname: Kazimirova
authors.forename: Miroslava
authors.initials: M
authors.lastname: Kuricova
authors.forename: Magdalena
authors.initials: M
authors.lastname: Barancokova
authors.forename: Aurelia
authors.initials: A
authors.lastname: Liskova
authors.forename: Eva
authors.initials: E
authors.lastname: Neubauerova
authors.forename: Martina
authors.initials: M
authors.lastname: Drlickova
authors.forename: Fedor
authors.initials: F
authors.lastname: Ciampor
authors.forename: Ivo
authors.initials: I
authors.lastname: Vavra
authors.forename: Dagmar
authors.initials: D
authors.lastname: Bilanicova
authors.forename: Giulio
authors.initials: G
authors.lastname: Pojana
authors.forename: Marta
authors.initials: M
authors.lastname: Staruchova
authors.forename: Mira
authors.initials: M
authors.lastname: Horvathova
authors.forename: Eva
authors.initials: E
authors.lastname: Jahnova
authors.forename: Katarina
authors.initials: K
authors.lastname: Volkovova
authors.forename: Maria
authors.initials: M
authors.lastname: Bartusova
authors.forename: Michal
authors.initials: M
authors.lastname: Cagalinec
authors.forename: Maria
authors.initials: M
authors.lastname: Dusinska
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D009152:Mutagenicity Tests; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010587:Phagocytosis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000633:toxicity*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: PLGA-PEO nanoparticles; genotoxicity; immunotoxicity; lymphocytes; natural killer cells; phagocytes and respiratory burst