Chitosan nanoparticles and their Tween 80 modified counterparts disrupt the developmental profile of zebrafish embryos.
Chitosan nanoparticles (CS-NPs) and their Tween 80 modified counterparts (TmCS-NPs) are among the most commonly used brain-targeted vehicles. However, their potential developmental toxicity is poorly understood. In this study, zebrafish embryos are introduced as an in vivo platform. Both NPs showed a dose-dependent increase in developmental toxicity (decreased hatching rate, increased mortality and incidences of malformation). Neurobehavioral changes included decreased spontaneous movement in TmCS-NP treated embryos and hyperactive effect in CS-NP treated larvae. Both NPs remarkably inhibited axonal development of primary and secondary motor neurons, and affected the muscle structure. Overall, this study demonstrated that CS-NPs and TmCS-NPs could affect embryonic development, disrupt neurobehavior of zebrafish larvae and affect muscle and neuron development, suggesting more attention on biodegradable chitosan nanoparticles.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China, PR China.
Zhongyue
Z
Yuan
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China, PR China.
Ying
Y
Li
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China, PR China.
Yulan
Y
Hu
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China, PR China.
Jian
J
You
Department of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Kazuma
K
Higashisaka
Department of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Kazuya
K
Nagano
Department of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Yasuo
Y
Tsutsumi
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China, PR China. Electronic address: gaojianqing@zju.edu.cn.
Jianqing
J
Gao
D000818:Animals; D048271:Chitosan / Q000009:adverse effects* / Q000737:chemistry; D047108:Embryonic Development / Q000187:drug effects*; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D009132:Muscles / Q000187:drug effects; D053758:Nanoparticles / Q000009:adverse effects* / Q000737:chemistry; D009474:Neurons / Q000187:drug effects; D011136:Polysorbates / Q000009:adverse effects* / Q000737:chemistry; D015027:Zebrafish / Q000254:growth & development*
D011136:Polysorbates; D048271:Chitosan
Chitosan nanoparticles; Developmental; Developmental neurotoxicity; Tween 80; Zebrafish