Functionalization of liposomes containing metformin and paclitaxel with trastuzumab: development, characterization and evaluation of efficacy against breast cancer

• Grant number: 13/05362-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 03, 2014
• End date: January 02, 2015
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Juliana Maldonado Marchetti
• Grantee: Josimar de Oliveira Eloy
• Supervisor: Robert J. Lee
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Ohio State University, Columbus, United States
• Associated to the scholarship: 12/10388-3 - Liposomes and immunoliposomes containing anticancer drugs: development, characterization and efficacy evaluation against breast cancer, BP.DR

Abstract

Breast cancer represents an important problem in public health, being one of the leading causes of death among women. 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. Recently, the observation that diabetic patients under treatment with metformin had better responses to cancer treatment stimulated investigation on its use in the treatment of this neoplasia, which has been presenting promising results. 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 functionalize with trastuzumab previously developed and characterized liposomes containing paclitaxel and metformin. Physical chemical characterization will involve the evaluation of antibody integrity, particle size measurement, zeta potential determination, morphology determination using transmission electronic microscopy. Cellular uptake and localization of the liposomes will be evaluated using confocal microscopy. The safety and efficacy evaluation of immunoliposomes will employ cytotoxicity studies and in vivo therapeutic evaluation, using xenograft animal models (AU)

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, NOV 1 2014. (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, 2017. (12/10388-3, 12/21513-3, 13/05362-8)

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, 2014. (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, 2015. (12/10388-3, 13/05362-8, 13/15134-2, 12/23764-3)

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, MAY 1 2016. (14/08462-6, 13/05362-8, 12/21513-3, 12/10388-3)