Toxicity of cationic solid lipid nanoparticles in rats

Autor(es)

Mendonca, M. C. P. ; Radaic, A. ; Fossa, F. G. ; Cruz-Hofling, M. A. ; de Jesus, M. B. ; IOP

• Tipo de documento: Artigo Científico
• Fonte: WAKE CONFERENCE 2021; v. 1323, p. 6-pg., 2019-01-01.

Resumo

Cationic solid lipid nanoparticles (cSLNs) represent one alternative to deliver poorly water-soluble drugs and oligonucleotides (e.g., DNA, siRNA, miRNA) based on well-known biocompatible and safe excipients. However, to guarantee the translation of cSLNs from the bench to bedside it is necessary to confirm that the formulation is safe. Hence, we investigate the toxicity of cSLNs formulation in adult male Wistar rats 24 h and 72 h after single intravenous injection (5 mL/kg b.w.). Hematological, biochemical and histopathological evaluation of the reticuloendothelial system and clearance organs indicated short-lived alterations including neutrophilia, a decrease in blood urea nitrogen levels, and an increase of the marginated pools of neutrophils and macrophages located in the lungs, liver, and spleen. These findings were transient as none of them were observed in treated animals after 72 h. We also observed the ability of cSLNs to enter the brain parenchyma without disrupting the blood-brain barrier. Few minor and acute transient alterations were found, but overall, cSLNs showed to be highly biocompatible under the experimental conditions of this study, including the capability of delivering into the central nervous system. The mechanistic understanding of biocompatibility and toxicity of cSLNs is needed for providing a safe clinical translation. (AU)

• Processo FAPESP: 14/03002-7 - Internalização e tráfego intracelular de nanopartículas: atividade biológica e perfil nanotoxicológico
• Beneficiário: Marcelo Bispo de Jesus
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 16/03765-6 - Determinação in vitro e in vivo do perfil toxicológico de formulações utilizando nanotecnologia
• Beneficiário: Monique Culturato Padilha Mendonça
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado