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Particle and Fibre Toxicology

, 8:33

First Online: 20 November 2011Received: 04 April 2011Accepted: 20 November 2011

Abstract

BackgroundOur 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.

MethodsTwo nanoparticle doses were used for the study in ICR mice. The low dose 766 mg-kg.bw 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-kg.bw 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.

ResultsAfter 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.

ConclusionsThe results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g-kg.bw 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.

KeywordsTilmicosin hydrogenated castor oil HCO solid lipid nanoparticles SLN acute toxicity List of abbreviationsTil-HCO-SLNtilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles

LD50median lethal dose

SLNsolid lipid nanoparticles

HCOhydrogenated castor oil

PVAPolyvinyl alcohol

ASTaspartate aminotransferase

ALTserum alanine aminotransferas

ALPalkaline phosphatase

TBILtotal bilirubin

CHOLcholesterol esters

CREAcreatinine

BUNblood urea nitrogen

TPtotal proteins

ALBalbumin

GLBglobulin

GLUglucose

WBCwhite blood cells

RBCred blood cells

HCThaematocrit

MCVmean corpuscular volume

HGBhemoglobin

MCHmean corpuscular haemoglobin

MCHCmean corpuscular haemoglobin concentration

PLTblood platelet

MPVmean platelet volume

PCTplateletcrit

RDWred cell distribution width

NEUneutrophils

LYMlymphocytes

MONmonocytes

EOSeosinophils

BASbasophils.

Electronic supplementary materialThe online version of this article doi:10.1186-1743-8977-8-33 contains supplementary material, which is available to authorized users.

Shuyu Xie, Fenghua Wang contributed equally to this work.

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Autor: Shuyu Xie - Fenghua Wang - Yan Wang - Luyan Zhu - Zhao Dong - Xiaofang Wang - Xihe Li - WenZhong Zhou

Fuente: https://link.springer.com/







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