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Liposomes and immunoliposomes containing anticancer drugs: development, characterization and efficacy evaluation against breast cancer

Grant number: 12/10388-3
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2012
Effective date (End): July 31, 2016
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Juliana Maldonado Marchetti
Grantee:Josimar de Oliveira Eloy
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):13/05362-8 - Functionalization of liposomes containing metformin and paclitaxel with trastuzumab: development, characterization and evaluation of efficacy against breast cancer, BE.EP.DR


Breast cancer represents an important problem in public health, being one of the leading causes of death among women. The treatment of the pathology varies depending on the biochemical characteristics of the tumor. Among the drugs used in the therapy, one of the most employed is paclitaxel, a cytotoxic agent with high potency and efficacy; however, it is associated with several side effects, because of drug and also due to the formulation composition. Hydrocloride metformin, traditionally used to treat diabetes, has been reported as a promising drug for cancer treatment, although the drug is very hydrophilic. Another drug that should be highlighted is rapamycin, commonly used as a immunosuppressant, which has been shown to have potent anticancer activity, particularly against breast cancer. However, it is a lipophilic drug, undergoes erythrocytes sequestration and is chemically unstable, factors that compromise bioavailability. The association between paclitaxel with metformin or rapamycin could be useful to treat breast cancer. Cases of breast cancer with overexpression of HER2 receptor are also very aggressive and therapy with the antibody anti-HER2 has been used successfully. Still, this antibody, trastuzumab (Herceptin®), could be used in pharmaceutical technology to target delivery systems to the cancer cells, enabling site-specific drug release. Based on this, the purpose of the present project is to develop and characterize long-circulating liposomes, carrying paclitaxel, metformin and/or rapamycin. The developed system will be targeted with trastuzumab. Physical chemical characterization will involve the determination of encapsulation efficiency, evaluation of antibody integrity, particle size measurement, zeta potential determination, morphology determination using transmission electronic microscopy, analysis of FTIR, DSC, TGA and in vitro drug release profile. Cellular uptake and localization of the liposomes will be evaluated using confocal microscopy and flow cytometry. Finally, liposomes and immunoliposomes will be evaluated for breast cancer efficacy in vitro, in cells, and in vivo, in an animal model.

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Scientific publications (5)
(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)
ELOY, JOSIMAR OLIVEIRA; DE SOUZA, MARINA CLARO; PETRILLI, RAQUEL; ABRIATA BARCELLOS, JULIANA PALMA; LEE, ROBERT J.; MARCHETTI, JULIANA MALDONADO. Liposomes as carriers of hydrophilic small molecule drugs: Strategies to enhance encapsulation and delivery. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 123, p. 345-363, . (13/05362-8, 12/21513-3, 12/10388-3)
ELOY, JOSIMAR O.; PETRILLI, RAQUEL; BRUEGGEMEIER, ROBERT W.; MARCHETTI, JULIANA MALDONADO; LEE, ROBERT J.. Rapamycin-loaded Immunoliposomes Functionalized with Trastuzumab: A Strategy to Enhance Cytotoxicity to HER2-positive Breast Cancer Cells. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 17, n. 1, p. 48-56, . (12/10388-3, 12/21513-3, 13/05362-8)
ELOY, JOSIMAR O.; PETRILLI, RAQUEL; TOPAN, JOSE FERNANDO; RIBEIRO ANTONIO, HERITON MARCELO; ABRIATA BARCELLOS, JULIANA PALMA; CHESCA, DEISE L.; SERAFINI, LUCIANO NEDER; TIEZZI, DANIEL G.; LEE, ROBERT J.; MARCHETTI, JULIANA MALDONADO. Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 141, p. 74-82, . (14/08462-6, 13/05362-8, 12/21513-3, 12/10388-3)
PETRILLI, RAQUEL; ELOY, JOSIMAR O.; MARCHETTI, JULIANA M.; LOPEZ, RENATA F. V.; LEE, ROBERT J.. Targeted Lipid Nanoparticles for Antisense Oligonucleotide Delivery. CURRENT PHARMACEUTICAL BIOTECHNOLOGY, v. 15, n. 9, p. 847-855, . (12/10388-3, 13/05362-8, 13/15134-2, 12/23764-3)
ELOY, JOSIMAR O.; PETRILLI, RAQUEL; LOPEZ, RENATA F. V.; LEE, ROBERT J.. Stimuli-Responsive Nanoparticles for siRNA Delivery. CURRENT PHARMACEUTICAL DESIGN, v. 21, n. 29, p. 4131-4144, . (12/10388-3, 13/05362-8, 13/15134-2, 12/23764-3)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ELOY, Josimar de Oliveira. Liposomes and immunoliposomes containing antitumor drugs: development, characterization and evaluation of the efficacy against breast cancer. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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