In situ gelling delivery systems for siRNA: development, characterization and study of in vitro and in vivo in animal model

• Grant number: 10/11736-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2011
• End date: July 31, 2012
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Vitória Lopes Badra Bentley
• Grantee: Lívia Neves Borgheti Cardoso
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The evidence that siRNA can be used for suppression of genes in different mammalian cells has attracted great attention as a new possibility of treatment for many diseases.However, for therapeutic application of siRNA is necessary to develop an effective and non-toxic delivery system, allowing uptake cell and prevent degradation by enzymes. One of the dosage forms that have been widely used in literature in order to protect and prolong the release of drugs and peptides are the formulations that form in situ gelling. Thus this project aims the pharmaceutical development of liquid crystalline formulations with gel formation in situ after subcutaneous administration to delivery siRNA, as well as the in vitro evaluation of their retention / release and toxicity. The specific objectives are: (1) Obtainment and characterization of liquid crystalline formulations that form gels in situ (2) Investigation of in vitro release of siRNA from these systems, (3) In vivo studies using an animal model for evaluation of gel formation in situ and (4) Study of toxicity in an animal model. This project is important because provide the basis for the application of siRNA as a therapeutic agent to treat serious diseases where gene therapy with RNAi is a treatment perspective.

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

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)

BORGHETI-CARDOSO, LIVIA NEVES; DEPIERI, LIVIA VIEIRA; DINIZ, HENRIQUE; JUNQUEIRA CALZZANI, RICARDO ALEXANDRE; DE ABREU FANTINI, MARCIA CARVALHO; IYOMASA, MAMIE MIZUSAKI; MOURA DE CARVALHO VICENTINI, FABIANA TESTA; LOPES BADRA BENTLEY, MARIA VITORIA. Self-assembling gelling formulation based on a crystalline-phase liquid as a non-viral vector for siRNA delivery. European Journal of Pharmaceutical Sciences, v. 58, p. 72-82, JUL 16 2014. (10/11736-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CARDOSO, Lívia Neves Borgheti. In situ gelling delivery systems for siRNA: development, characterization and studies in vitro and in vivo in animal model. 2012. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.