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

[Display omitted] 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 gelli...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2014-07, Vol.58, p.72-82
Main Authors: Borgheti-Cardoso, Lívia Neves, Depieri, Lívia Vieira, Diniz, Henrique, Calzzani, Ricardo Alexandre Junqueira, de Abreu Fantini, Márcia Carvalho, Iyomasa, Mamie Mizusaki, Moura de Carvalho Vicentini, Fabiana Testa, Bentley, Maria Vitória Lopes Badra
Format: Article
Language:English
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Summary:[Display omitted] 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 2h. 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 30days. 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.
ISSN:0928-0987
1879-0720
DOI:10.1016/j.ejps.2014.04.001