title: Biocompatibility evaluation of pH and glutathione-responsive nanohydrogels after intravenous administration.
abstract: Nanotoxicology has emerged as an important subdiscipline of nanotechnology due to the new healthy risks associated with the use of nanosystems for therapy and diagnostic. The biocompatibility of four stimuli-responsive nanohydrogel (NG) formulations based on different proportions of N-isopropylacrylamide (NIPA), N-hydroxyethyl acrylamide (HEAA) and 2-acrylamidoethyl carbamate (2AAECM), and cross-linked with N,N-cystaminebisacrylamide (CBA) or N-methylenebisacrylamide (NMBA) has been evaluated after intravenous injection in Wistar rats. All nanohydrogels were pH-sensitive, and those with CBA were also glutathione-responsive. Haematological and coagulation parameters revealed most nanogel formulations did not cause modification, only the NHA 80/15/5-CBA formulation induced a transitory light increase in platelets. Prothrombin time was in the reference normal range, there were no modifications of fibrinogen concentration and an increase in antithrombin III was observed on the last day of the study. Blood biochemical parameters such as AST, ALT, ALP, BUN, and creatinine were in the standard range for rats. The activity of enzyme antioxidant defences (SOD, CAT and GSSG-R) and total glutathione were evaluated in liver, kidney and spleen samples. Nanohydrogels cross-linked with the disulphide reducible CBA-cross-linker caused a decrease in GSSG/GSH content and an increase in GSSG-R activity in the spleen. The antioxidant response is also reflected by modifications of SOD activity in liver and kidney of NHA 80/15/5-CBA and NHA 80/10/10-NMBA groups. Histology showed no tissue damage, inflammation or morphological change in liver, kidney and spleen. Overall, the results demonstrated modifications of antioxidant defences; however, no acute or very significant changes in biomarkers of liver or kidney damage were observed.
authors.affiliation: Dpto. Bioquímica y Biología Molecular III, Facultad de Medicina, Ciudad Universitaria s/n, UCM, 28040 Madrid, Spain. Electronic address: elenpe01@ucm.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Pérez
authors.affiliation: Dpto. Bioquímica y Biología Molecular III, Facultad de Medicina, Ciudad Universitaria s/n, UCM, 28040 Madrid, Spain. Electronic address: rmolmo@med.ucm.es.
authors.forename: Rosa
authors.initials: R
authors.lastname: Olmo
authors.affiliation: Dpto. Enfermería, Facultad de Enfermería, Fisioterapia y Podología, Ciudad Universitaria s/n, UCM, 28040 Madrid, Spain. Electronic address: cteijon@enf.ucm.es.
authors.forename: César
authors.initials: C
authors.lastname: Teijón
authors.affiliation: Dpto. Biología Molecular (Morfología Microscópica), Facultad de Biología, Ciudad Universitaria s/n, UCM, 28040 Madrid, Spain. Electronic address: hernan@bio.ucm.es.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Muñíz
authors.affiliation: Dpto. Bioquímica y Biología Molecular III, Facultad de Medicina, Ciudad Universitaria s/n, UCM, 28040 Madrid, Spain. Electronic address: nmpastor@estumail.ucm.es.
authors.forename: Nuria
authors.initials: N
authors.lastname: Montero
authors.affiliation: Dpto. Bioquímica y Biología Molecular III, Facultad de Medicina, Ciudad Universitaria s/n, UCM, 28040 Madrid, Spain. Electronic address: jmt@med.ucm.es.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Teijón
authors.affiliation: Dpto. Bioquímica y Biología Molecular III, Facultad de Medicina, Ciudad Universitaria s/n, UCM, 28040 Madrid, Spain. Electronic address: mdblanco@med.ucm.es.
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Blanco
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001780:Blood Coagulation Tests; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D049329:Nanostructures; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione
keywords: Antioxidant defences; Biocompatibility; Coagulation; Haematology; Stimuli-responsive nanohydrogels