title: Accumulation of nanocarriers in the ovary: a neglected toxicity risk?
abstract: Several nanocarrier systems are frequently used in modern pharmaceutical therapies. Within this study a potential toxicity risk of all nanoscaled drug delivery systems was found. An accumulation of several structurally different nanocarriers but not of soluble polymers was detected in rodent ovaries after intravenous (i.v.) administration. Studies in different mouse species and Wistar rats were conducted and a high local accumulation of nanoparticles, nanocapsules and nanoemulsions in specific locations of the ovaries was found in all animals. We characterised the enrichment by in vivo and ex vivo multispectral fluorescence imaging and confocal laser scanning microscopy. The findings of this study emphasise the role of early and comprehensive in vivo studies in pharmaceutical research. Nanocarrier accumulation in the ovaries may also comprise an important toxicity issue in humans but the results might as well open a new field of targeted ovarian therapies.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schädlich
authors.forename: Stefan
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.forename: Henrike
authors.initials: H
authors.lastname: Caysa
authors.forename: Cornelia
authors.initials: C
authors.lastname: Rose
authors.forename: Achim
authors.initials: A
authors.lastname: Göpferich
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Judith
authors.initials: J
authors.lastname: Kuntsche
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005456:Fluorescent Dyes; D005470:Fluorometry; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000633:toxicity*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012306:Risk; D013045:Species Specificity; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes