Self-assembling gelling formulation based on a crystalline-phase liquid as a non-viral vector for siRNA delivery

Author(s)

Borgheti-Cardoso, Livia Neves ^[1] ; Depieri, Livia Vieira ^[1] ; Diniz, Henrique ^[1] ; Junqueira Calzzani, Ricardo Alexandre ^[2] ; de Abreu Fantini, Marcia Carvalho ^[3] ; Iyomasa, Mamie Mizusaki ^[2] ; Moura de Carvalho Vicentini, Fabiana Testa ^[1] ; Lopes Badra Bentley, Maria Vitoria ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Odontol Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Inst Fis, BR-01498 Sao Paulo - Brazil

• Document type: Journal article
• Source: European Journal of Pharmaceutical Sciences; v. 58, p. 72-82, JUL 16 2014.
• Web of Science Citations: 22

Abstract

Liquid crystalline systems (LCSs) form interesting drug delivery systems. These include in situ gelling delivery systems, which present several advantages for use as self-assembling systems for local drug delivery. The aim of this study was to develop and characterize in situ gelling delivery systems for local siRNA delivery. The influence of the components that form the systems was investigated, and the systems were characterized by polarized light microscopy, Small Angle X-ray Scattering (SAXS), swelling studies, assays of their ability to form a complex with genes and of the stability of the genes in the system, as well as assays of in situ gelling formation and local toxicity using an animal model. The system containing a mixture of monoglycerides (MO), oleylamine (OAM), propylene glycol (PG) and tris buffer (8.16:0.34:76.5:15, w/w/w/w) was considered the most appropriate for local siRNA delivery purposes. The molecular structure was characterized as hexagonal phase; the swelling studies followed a second order kinetic model and the water absorption was a fast process reaching equilibrium at 2 h. The system formed a complex with siRNA and remained in a stable form. The gel was formed in vivo after subcutaneous administration of a precursor fluid formulation in mice and was biodegradable in 30 days. The inflammatory process that took place was considered normal. Therefore, the developed liquid crystalline delivery system shows the appropriate characteristics for use as a local siRNA delivery method for gene therapy. (C) 2014 Elsevier B.V. All rights reserved. (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