title: Brain Localization and Neurotoxicity Evaluation of Polysorbate 80-Modified Chitosan Nanoparticles in Rats.
abstract: The toxicity evaluation of inorganic nanoparticles has been reported by an increasing number of studies, but toxicity studies concerned with biodegradable nanoparticles, especially the neurotoxicity evaluation, are still limited. For example, the potential neurotoxicity of Polysorbate 80-modified chitosan nanoparticles (Tween 80-modified chitosan nanoparticles, TmCS-NPs), one of the most widely used brain targeting vehicles, remains unknown. In the present study, TmCS-NPs with a particle size of 240 nm were firstly prepared by ionic cross-linking of chitosan with tripolyphosphate. Then, these TmCS-NPs were demonstrated to be entered into the brain and specially deposited in the frontal cortex and cerebellum after systemic injection. Moreover, the concentration of TmCS-NPs in these two regions was found to decrease over time. Although no obvious changes were observed for oxidative stress in the in vivo rat model, the body weight was found to remarkably decreased in a dose-dependent manner after exposure to TmCS-NPs for seven days. Besides, apoptosis and necrosis of neurons, slight inflammatory response in the frontal cortex, and decrease of GFAP expression in the cerebellum were also detected in mouse injected with TmCS-NPs. This study is the first report on the sub-brain biodistribution and neurotoxicity studies of TmCS-NPs. Our results provide new insights into the toxicity evaluation of nanoparticles and our findings would help contribute to a better understanding of the neurotoxicity of biodegradable nanomaterials used in pharmaceutics.
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
authors.forename: Zhong-Yue
authors.initials: ZY
authors.lastname: Yuan
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Hu
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes; D011136:Polysorbates; D048271:Chitosan