In vivo evaluation of in situ gelling systems to treatment of squamous cell carcinoma after intratumoral administration

• Grant number: 13/02132-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2013
• End date: August 31, 2014
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Vitória Lopes Badra Bentley
• Grantee: Lívia Neves Borgheti Cardoso
• Supervisor: Raymond M. Schiffelers
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Utrecht University (UU), Netherlands
• Associated to the scholarship: 12/15341-5 - In situ gelling liquid crystalline system of intratumoral administration for sustained release of siRNA in skin cancer therapy., BP.DR

Abstract

The discovery that siRNA can be used for gene inhibition in different mammalian cells by a mechanism known as RNA interference, which is an event of gene repression through the degradation of messenger RNA, has attracted huge attention as new possibility for the treatment of several serious diseases like cancer. However, for siRNA effective therapeutic application is necessary to develop non-toxic delivery systems that should be able to release the siRNA into target cells, promote it cellular internalization and prevent it degradation. The ability of gene suppression promoted by siRNA depends both on the number of siRNA molecules transfected into the cell and on cell doubling rate, therefore, for cancer treatment, which there are high cell proliferation, is interesting the development of systems that promote a sustained release of siRNA. An interesting delivery system with this characteristic is the lipid or amphiphilic-based liquid formulation that in situ gelling by self-assembling mechanism, in this case shown by water absorption of the biological environment in the administration site. The in situ gelling systems that are going to use in this research project were chosen from the results obtained so far and were able to form complexes with siRNA, being biocompatible and biodegradable. Thereby, during the internship in University Medical Center Utrecht is going to be evaluated intratumoral gel formation as well as determined the in vivo siRNA profile release and evaluated the effectiveness of in situ gelling liquid crystal-based systems complexed with EGFRsiRNA in the treatment of squamous cell carcinoma after intratumoral administration. This project is a new promising approach for gene therapy of skin cancer. (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)

BORGHETI-CARDOSO, LIVIA N.; KOOIJMANS, SANDER A. A.; FENS, MARCEL H. A. M.; VAN DER MEEL, ROY; VICENTINI, FABIANA T. M. C.; FANTINI, MARCIA C. A.; BENTLEY, MARIA VITORIA L. B.; SCHIFFELERS, RAYMOND M.. In Situ Gelling Liquid Crystalline System as Local siRNA Delivery System. MOLECULAR PHARMACEUTICS, v. 14, n. 5, p. 1681-1690, MAY 2017. (13/02132-1)

BORGHETI-CARDOSO, LIVIA NEVES; DEPIERI, LIVIA VIEIRA; KOOIJMANS, SANDER A. A.; DINIZ, HENRIQUE; JUNQUEIRA CALZZANI, RICARDO ALEXANDRE; MOURA DE CARVALHO VICENTINI, FABIANA TESTA; VAN DER MEEL, ROY; DE ABREU FANTINI, MARCIA CARVALHO; IYOMASA, MAMIE MIZUSAKI; SCHIFFELERS, RAYMOND M.; et al. An in situ gelling liquid crystalline system based on monoglycerides and polyethylenimine for local delivery of siRNAs. European Journal of Pharmaceutical Sciences, v. 74, p. 103-117, JUL 10 2015. (10/11736-0, 13/02132-1)