Preparation of immunoliposomes for topical skin cancer treatment

• Grant number: 13/15134-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): January 03, 2014
• Effective date (End): January 02, 2015
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Renata Fonseca Vianna Lopez
• Grantee: Raquel Petrilli
• Supervisor: Robert J. Lee
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Ohio State University, Columbus, United States
• Associated to the scholarship: 12/23764-3 - Topical application of liposomes containing Cetuximab: the effect of physical skin penetration enhancement techniques for cutaneous squamous cell carcinoma, BP.DR

Abstract

Among skin cancers, the squamous cell carcinoma (SCC) holds the second position in frequency and is biologically more aggressive than the basocelular skin cancer. SCC over-expresses the epidermal growth factor receptor (EGFR), which is responsible for communicating extracellular signals to the nucleus and is commonly associated with bad prognosis. The interruption of the signaling cell pathway by the administration of the anti-EGFR cetuximab is a current strategy to inhibit tumor growth. The topical chemotherapy of these tumors is a promising strategy for the reduction of the side effects associated to this kind of therapy. However, to reach the SCC, the drug needs to overcome the primary skin barrier, the stratum corneum (SC). The use of physical methods, such as iontophoresis and low frequency ultrasound (LFS), is then necessary to disturb the SC and allows the cetuximab to reach the tumor cells in high concentrations. Furthermore, the antibody activity is conformation dependent, which means that aggregation changes cetuximab interactions with EGFR. Therefore, topical administration of cetuximab likely requires a delivery system. In this context, the aim of this work is to study different strategies, such as LFS, iontophoresis and drug delivery systems, to topically deliver cetuximab for skin SCC treatment. Liposomes encapsulated or covalently bound to cetuximab will be developed under Prof Robert Lee supervision. Under Prof. Lopez supervision, the influence of LFS and iontophoresis in the tumoral penetration of the drug will be assessed and the efficacy of the drug delivery systems developed will be investigated in vivo using an animal xenograft model for the disease. (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)

PETRILLI, RAQUEL; ELOY, JOSIMAR O.; LOPEZ, RENATA F. V.; LEE, ROBERT J.. Cetuximab Immunoliposomes Enhance Delivery of 5-FU to Skin Squamous Carcinoma Cells. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 17, n. 2, p. 301-308, 2017. (13/15134-2, 12/23764-3, 14/22451-7)

PETRILLO, R.; ELOY, J. O.; PASCHOAL, J. A. R.; LOPEZ, V, R. F.. Quantification of 5-FU in skin samples for the development of new delivery systems for topical cancer treatment. Pharmazie, v. 73, n. 3, p. 133-138, MAR 2018. (14/22451-7, 13/15134-2, 12/23764-3)

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, 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)

PETRILLI, RAQUEL; ELOY, JOSIMAR O.; SAGGIORO, FABIANO P.; CHESCA, DEISE L.; DE SOUZA, MARINA CLARO; DIAS, MARCOS V. S.; DASILVA, LUIS L. P.; LEE, ROBERT J.; LOPEZ, RENATA F. V.. Skin cancer treatment effectiveness is improved by iontophoresis of EGFR-targeted liposomes containing 5-FU compared with subcutaneous injection. JOURNAL OF CONTROLLED RELEASE, v. 283, p. 151-162, AUG 10 2018. (14/22451-7, 13/15134-2, 12/23764-3)