Open Access Research

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

Shuyu Xie1, Fenghua Wang1, Yan Wang1, Luyan Zhu1, Zhao Dong1, Xiaofang Wang1, Xihe Li2 and WenZhong Zhou1*

Author Affiliations

1 Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan Road West, Beijing 100193, PR China

2 Inner Mongolia Saikexing Reproductive Biotechnology Co. Ltd./Inner Mongolia University College of Life Sciences, Mengniu Dary R&D Center, Shengle Economic District, Helin Geer, Huhhot, Inner Mongolia 011517, PR China

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Particle and Fibre Toxicology 2011, 8:33  doi:10.1186/1743-8977-8-33

Published: 20 November 2011



Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN.


Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/ with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/ was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters.


After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group.


The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/ and thus the nanoparticles are considered low toxic according to the toxicity categories of chemicals. Moreover, HCO-SLN significantly decreased the toxicity of tilmicosin. Normal clinic dosage of Til-HCO-SLN is safe as evaluated by acute toxicity.

Tilmicosin; hydrogenated castor oil (HCO); solid lipid nanoparticles (SLN); acute toxicity