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Folate-targeted polymeric nanoparticles for ovarian cancer

Grant number: 16/06369-4
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): August 11, 2016
Effective date (End): December 10, 2016
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Juliana Maldonado Marchetti
Grantee:Juliana Palma Abriata
Supervisor abroad: Robert J Lee
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : Ohio State University, Columbus, United States  
Associated to the scholarship:13/22747-0 - Development and characterization of nanoparticles with polycaprolactone containing paclitaxel targeted with bevacizumab for optimization of ovarian cancer therapy, BP.DR

Abstract

Ovarian cancer (adenocarcinoma) occurs in 50% of cases of malignant tumors of the ovaries and presents bilaterally in 30-50% of patients. The highest lethality of this cancer is due to late diagnosis. In Brazil, 6,000 new cases were estimated in 2012, and in 2010, there were approximately 3,000 deaths. This type of cancer tends to be aggressive and does not have a test to detect "early" and most patients when diagnosed are in stage III and IV of the disease, stage which cancer is spread into the peritoneal cavity . Although paclitaxel is the drug of choice for the treatment of ovarian cancer, this drug has low aqueous solubility which reduces its bioavailability. Therefore, new formulations have been developed, Taxol®, despite increasing solubility of paclitaxel presents high toxicity due to a mixture of ethanol and Cremophor EL®, causing various toxic side effects. In addition, the resistance to this treatment occurs in more than 70% of patients. Thus, the development of new formulations with paclitaxel is very relevant. Nanotechnology has been widely used for the placement of several drugs and a new generation of site-specific nanoparticles have been developed allowing an increase in permeability and retention effect (EPR) in the tumor vasculature, enhancing the penetration of active anti-cancer drugs. The delivery can be increased through functionalization by attaching antibodies or other ligands, such as those ones that recognize tumor-associated antigen, increasing exposure to malignant cells and decreasing the exposure to the normal cells. Based on these, the aim of this work is to develop and characterize polymeric nanoparticles containing paclitaxel, functionalize them with folate, aiming to optimize the treatment of ovarian cancer, assessed by cell culture and in vivo efficacy study in animal model. Briefly, the polycaprolactone-PEG-folato will be prepared and characterize by FTIR. Subsequently, the PN-PEG-FOL will be evaluated through particle size, zeta potential and particle concentration.