Abstract

Layered double hydroxide (LDH) nanoparticles, also known as anionic clays, have attracted a great deal of interest for their potential as delivery carriers. Recent studies showed that LDH nanoparticles can efficiently deliver drugs or bioactive molecules into cells, which are highly related to their endocytic pathway. However, the efficient cell permeation capacity of LDH may also raise concern about their toxicity potential. In this study, the acute oral toxicity of LDH nanoparticles was assessed, and their kinetic behaviors, such as plasma concentration-time curve, tissue distribution, and excretion, were also evaluated in mice. No significant effects of oral LDH nanoparticles on behaviors, body weight gain, survival rate, and organosomatic index were observed up to the dose of 2000 mg/kg for 14 days. Serum biochemical parameters did not significantly increase, indicating that LDH nanoparticles did not cause acute liver or kidney injury. Plasma concentration of LDH nanoparticles rapidly decreased within 30 min depending on exposure doses, but they did not accumulate in any specific organ. Their excretion via urine and feces was observed within 24 h. These findings suggest that LDH nanoparticles do not exhibit acute oral toxicity and favorable kinetic behaviors in mice and, therefore, will be promising candidates for biological and pharmaceutical applications.

Highlights

  • In recent years, inorganic nanomaterials have been extensively developed for biomedical applications, such as diagnostic or imaging agents, tissue engineering, and drug delivery carriers [1,2,3]

  • The acute oral toxicity of Layered double hydroxide (LDH) nanoparticles of about 100 nm was evaluated after administration of four different doses (5, 50, 300, and 2000 mg/kg) in mice

  • The results demonstrated that LDH nanoparticles did not cause any mortality, abnormal behaviors, symptoms, and body weight loss up to the highest dose administered, indicating that the LD50 values were more than 2000 mg/kg

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Summary

Introduction

Inorganic nanomaterials have been extensively developed for biomedical applications, such as diagnostic or imaging agents, tissue engineering, and drug delivery carriers [1,2,3]. Nanoparticles have large surface areas and high reactivity resulting from their small size. Their structure can be modified for target specific delivery [4]. This is fascinating to efficiently deliver target molecules to specific organs and contributing to enhanced efficacy as well as reduced toxicity. Recent studies have demonstrated that LDHs can efficiently deliver anticancer drugs or bioactive molecules into cells, leading to enhanced efficacy of intercalated molecules, which are closely related to their energydependent endocytic pathway, clathrin-mediated endocytosis [9,10,11]. The efficient cell permeation capacity of LDHs may cause undesirable harmful effects by interfering with biological cellular functions, which raises concern about their toxicity potential on human health

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