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

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Author(s):
Juliana Palma Abriata
Total Authors: 1
Document type: Doctoral Thesis
Press: Ribeirão Preto.
Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto
Defense date:
Examining board members:
Juliana Maldonado Marchetti; Talita Mota Gonçalves; Marilisa Guimarães Lara; Monica Maruno; Eduardo Ricci Junior
Advisor: Juliana Maldonado Marchetti; Priscyla Daniely Marcato Gaspari
Abstract

Adenocarcinoma occurs in 90% of cases of malignant ovarian cancer and is present bilaterally in 30 to 50% of patients. Due to lack of initial symptoms and the low specificity of the existing tumor markers, the cancer is detected when it\'s in stages III and IV, which indicate spread into the peritoneal cavity. Paclitaxel (PCX) is the drug of first choice for ovarian cancer treatment, but it has low aqueous solubility, which reduces its bioavailability. Thus, in the commercial drug, Taxol®, PCX is solubilized in a mixture of toxic surfactants. The development of drug nanocarriers has been investigated to promote the reduction of toxic effects and increase the safety and therapeutic efficacy of PCX. Functionalization of nanocarriers is one of the strategies used to increase selectivity to tumor cells that overexpress folate receptors. The aim of the present work was the development and characterization of folate-modified nanoparticles (NPPCX-AF) and unmodified nanoparticles (NPPCX) and evaluation of in vitro efficacy of developed systems using adenocarcinoma cell lines. The systems were successfully obtained using nanoprecipitation technique. The results showed that the NPPCX and NPPCX-AF formulations had a particle size distribution of 140 and 154.6 nm, respectively, and polydispersity indexes smaller than 0.1, with high PCX encapsulation efficiency. The results obtained were suitable for the intravenous administration route and promotion of active targeting in the tumor microenvironment. The in vitro cellular cytotoxicity assays of SKOV-3 and OVCAR-3 cell lines demonstrated that NPPCX and NPPCX-AF were able to release PCX and reduce cell viability. The flow cytometry assays demonstrated that both nanoparticles presented a time dependent cellular uptake, showing the ability of nanocarriers to be uptake. In addition, comparing both cell lines, SKOV-3 showed a higher uptake due to its greater amount of folate receptors. Thus, in vitro results suggested that the nanocarriers, NPPCX and NPPCX-AF, present a distinguish potential for ovarian cancer therapy optimization. In vivo studies are needed to confirm the in vitro results and provide additional data regarding safety and efficacy of ovarian cancer treatment. (AU)

FAPESP's process: 13/22747-0 - Development and characterization of nanoparticles with polycaprolactone containing paclitaxel targeted with bevacizumab for optimization of ovarian cancer therapy
Grantee:Juliana Palma Abriata
Support type: Scholarships in Brazil - Doctorate