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The in vivo toxicological profile of cationic solid lipid nanoparticles

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Abstract

Cationic solid lipid nanoparticles (cSLNs) are considered as one of the most effective lipid nanocarriers for delivery of low water-solubility compounds and genetic materials. As the excipients used in the cSLN production are generally regarded as safe (GRAS), the formulations are granted as non-toxic. However, the toxicological profile of new SLN-based formulations should always be performed to confirm that the delivery systems themselves may not impose risks to the human health. Therefore, in this study, we delineate the toxicological profile of the cSLN formulation at 24 and 72 h after single intravenous injection to male Wistar rats. Hematological, biochemical, and histopathological evaluations of the spleen, lungs, liver, and kidneys indicated short-lived alterations including neutrophilia. We found increases in the population of macrophages in the lungs, liver, and spleen and also migration of circulating neutrophils into inflamed tissue and a decrease in blood urea nitrogen. We also observed the presence of cSLNs within the brain parenchyma without any sign of damage to the blood-brain barrier. These side effects appeared to be mild and transitory (< 72 h). These findings reinforce the importance of investigating the toxicity of SLN-based formulations before the incorporation of drugs/genetic material to the formulation and its translation to the clinic.

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Abbreviations

ALB:

Albumin

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

BBB:

Blood-brain barrier

BUN:

Blood urea nitrogen

CRE:

Creatinine

cSLNs:

Cationic solid lipid nanoparticles

DAPI:

4′,6-Diamidino-2-phenylindole

FDA:

Food and Drug Administration

GRAS:

Generally regarded as safe

Hb:

Hemoglobin

Hct:

Hematocrit

MCH:

Mean corpuscular hemoglobin

MCHC:

Mean corpuscular hemoglobin concentration

MCV:

Mean corpuscular volume

OCT:

Optimal cutting temperature

PBS:

Phosphate-buffered saline

PDI:

Polydispersity index

PFA:

Paraformaldehyde

PLT:

Platelet

RBCs:

Red blood cells

RECA-1:

Rat endothelial cell antibody-1

RES:

Reticuloendothelial system

SLNs:

Solid lipid nanoparticles

TB:

Total bilirubin

TBS:

Tris-buffered saline

WBCs:

White blood cells

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Acknowledgments

We thank the access to equipment and assistance provided by the National Institute of Science and Technology on Photonics Applied to Cell Biology (INFABIC) at the University of Campinas.

Funding

This research was supported by the Brazilian funding agencies: São Paulo Research Foundation (FAPESP) (grants #2016/03765-6 and #2014/03002-7) and National Council for Scientific and Technological Development (CNPq) (grants #305099/2011-6 and #310111/2016-4).

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Contributions

AR and MBJ designed the idea of the study. AR and FF were involved in particle synthesis and characterization, and assisted in manuscript revision. MCPM carried out all biological experimentation and wrote the manuscript. MCPM and AR performed the hematological and biochemistry analysis. FF performed the immunofluorescence staining and assisted the confocal imaging. MACH and MARV offered laboratory facilities and were involved in the writing of the manuscript. MBJ supervised the project and revised the manuscript. All authors have read and approved the final manuscript version.

Corresponding author

Correspondence to Marcelo Bispo de Jesus.

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Mendonça, M.C.P., Radaic, A., Garcia-Fossa, F. et al. The in vivo toxicological profile of cationic solid lipid nanoparticles. Drug Deliv. and Transl. Res. 10, 34–42 (2020). https://doi.org/10.1007/s13346-019-00657-8

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