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

Author(s)

Livia Neves Borgheti Cardoso

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2012-08-02

Examining board members

Maria Vitoria Lopes Badra Bentley; Osvaldo de Freitas; Frederico Marianetti Soriani

• Advisor: Maria Vitoria Lopes Badra Bentley

Abstract

The evidence that siRNA can be used for suppression of genes in different mammalian cells attracted wide attention as a new possibility of treatment for various diseases. However, for siRNA therapeutic application is necessary to develop an effective non-toxic delivery system, which facilitate the siRNA cell uptake and avoid its degradation by enzymes. The genes suppression promoted by siRNA depends on the number of siRNA molecules transfected as the cell replication rate. One of the dosage forms that have been widely used in literature in order to prolong and protect the drug release is the in situ gelling formulations. Thus, the present study aimed the development and characterization of the in situ gelling liquid crystal-based systems for subcutaneous application of siRNA in gene therapy. Appropriate mixtures of monoolein, propylene glycol, Tris buffer and polyethyleneimine or oleylamine (cationic polymer and lipid, respectively) was able to form precursor formulation that gelling in water excess and, as demonstrated by the swelling studies, the gel formation is a fast process. The developed formulations were also effective for complexing the siRNA, indicating the importance of the incorporation of cationic additives in the systems. The in vitro release study showed that the release is dependent on the water absorption rate. In vivo studies in animal models have shown the gel is formed in vivo after water uptake of body fluids, and it is biodegradable and biocompatible. The systems developed are promising for the treatment of diseases where the local and sustained administration of siRNA is necessary. (AU)

• FAPESP's process: 10/11736-0 - In situ gelling delivery systems for siRNA: development, characterization and study of in vitro and in vivo in animal model
• Grantee: Lívia Neves Borgheti Cardoso
• Support Opportunities: Scholarships in Brazil - Master