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Systemic toxicity induced by aggregated layered double hydroxide nanoparticles

Authors Yan M, Yang C, Huang B, Huang Z, Huang L, Zhang X, Zhao C

Received 14 July 2017

Accepted for publication 6 September 2017

Published 3 October 2017 Volume 2017:12 Pages 7183—7195

DOI https://doi.org/10.2147/IJN.S146414

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang


Mina Yan, Chanzhen Yang, Binyao Huang, Zeqian Huang, Liangfeng Huang, Xuefei Zhang, Chunshun Zhao

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou Higher Education Mega Center, Guangzhou, China

Abstract: Layered double hydroxide (LDH) nanoparticles are emerging as one of the promising nanomaterials for biomedical applications, but their systemic toxicity in vivo has received little attention. In the present study, the effects of inorganic nanoparticle aggregation on their systemic toxicity were examined. Remarkably, aggregation was observed after the mixing of naked LDH nanoparticles with saline or erythrocytes. Significant accumulation of the naked LDH nanoparticles in the lungs of mice was detected 1 h after intravenous administration, and the survival rate of mice was 0% after 6 repeated injections. Furthermore, flocculent precipitates in the alveoli and congestion in the lung interstitium were observed in the dead mice. However, lipid membrane-coated LDH nanoparticles would not form aggregates and could be injected intravenously >6 times without causing death. These findings suggested that repeated injections of LDH were lethal even at low dose (30 mg/kg), and lipid membrane coating can be considered as an approach for reducing this risk.

Keywords: inorganic nanoparticles, aggregation, erythrocyte aggregation, repeated intravenous injection, pulmonary embolism, sudden death

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