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Development and characterization of nanoparticles with polycaprolactone containing paclitaxel targeted with bevacizumab for optimization of ovarian cancer therapy

Grant number: 13/22747-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2015
Effective date (End): February 01, 2018
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Juliana Maldonado Marchetti
Grantee:Juliana Palma Abriata
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):16/06369-4 - Folate-targeted polymeric nanoparticles for ovarian cancer, BE.EP.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, approximately 3,000 deads. This type of cancer tends to be aggressive and do 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 with the newer drug, Taxol ®, despite increasing solubility of paclitaxel presents high toxicity to contain a mixture of ethanol and Cremophor EL® and this emulsifying agent provides 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, assisting the penetration of active anti-cancer drugs. This targeting can be increased by attaching antibodies or other ligands 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, functionalized with monoclonal anti-HER2 bevacizumab, aiming to optimize the treatment of ovarian cancer, assessed by cell culture and animal model. The physicochemical characterization involve the determination of encapsulation efficiency of the drug, assessing the integrity of the antibody after conjugation to the polymeric nanoparticle measure particle size and zeta potential, morphology observation by scanning electron microscopy and transmission and in vitro determination release profile of paclitaxel . The immune-nanoparticles will be evaluated for efficacy and cytotoxicity of the systems obtained in strains of normal and tumor cells by MTT and flow cytometry, and in vivo model from the chemical induction of ovarian cancer. Finally, histopathological evaluation and analysis of the toxicity of the developed formulations will be performed. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ABRIATA, JULIANA PALMA; TURATTI, ROGER CASANOVA; LUIZ, MARCELA TAVARES; RASPANTINI, GIOVANNI LOUREIRO; TOFANI, LARISSA BUENO; FERRAZ DO AMARAL, ROBSON LUIS; SWIECH, KAMILLA; MARCATO, PRISCYLA DANIELY; MARCHETTI, JULIANA MALDONADO. Development, characterization and biological in vitro assays of paclitaxel-loaded PCL polymeric nanoparticles. Materials Science & Engineering C-Materials for Biological Applications, v. 96, p. 347-355, MAR 2019. Web of Science Citations: 4.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ABRIATA, Juliana Palma. Development and characterization of polycaprolactone nanoparticles containing paclitaxel targeted with folate for ovarian cancer therapy optimization. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Ribeirão Preto.

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