Effect of administration of paclitaxel bound to cholesterol nanoparticles in experimental model of kidney transplantation in rats

• Grant number: 15/24569-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2016
• End date: March 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Irene de Lourdes Noronha
• Grantee: Natália de Carvalho Maffei
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Kidney transplantation is recognized as one of the best treatment options for patients with chronic kidney disease at an advanced stage. However, despite advances in organ transplant practice, it is still limited the long-term success of this treatment modality. Acute allograft rejection is still a major problem for successful long-term transplantation. Thus, strategies to block the acute rejection of renal allograft are of utmost importance. The paclitaxel linked to nanoparticles of LDE (nanoPACLI), has a higher specificity compared to the free drug, acting locally and more precisely, and prevent complications caused by its systemic administration. Therefore, the aim of this study is to analyze the effect of paclitaxel linked to LDE in renal transplant model in rats. Kidney transplantation in mice is carried out using the isogenic strains Dark Agouti (DA) as donors and Lewis (LEW) as receivers. Three groups will be formed: ISO, LEW-LEW transplant, ALO + nano, DA-LEW transplant will receive only LDE nanoparticles, and ALO + nanoPACLI, DA-LEW transplant treated with paclitaxel nanoparticles linked to LDE. After 10 days of transplantation, the animals will be euthanized and the grafts will be taken for histological analysis. It will also be performed immuno histochemistry for macrophages and lymphocytes and PCR for pro-inflammatory mediators (TNF-±, IL-1ß, IFN-³ and T-bet) and Th2 profile (IL-4, IL-10 and GATA-3) in renal allograft by analyzing the gene expression real-time PCR.