title: Self-assembling gelling formulation based on a crystalline-phase liquid as a non-viral vector for siRNA delivery.
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.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Lívia Neves
authors.initials: LN
authors.lastname: Borgheti-Cardoso
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Lívia Vieira
authors.initials: LV
authors.lastname: Depieri
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Henrique
authors.initials: H
authors.lastname: Diniz
authors.affiliation: Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Ricardo Alexandre Junqueira
authors.initials: RA
authors.lastname: Calzzani
authors.affiliation: Instituto de Física, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Márcia Carvalho
authors.initials: MC
authors.lastname: de Abreu Fantini
authors.affiliation: Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Mamie Mizusaki
authors.initials: MM
authors.lastname: Iyomasa
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Fabiana Testa
authors.initials: FT
authors.lastname: Moura de Carvalho Vicentini
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil. Electronic address: vbentley@usp.br.
authors.forename: Maria Vitória Lopes Badra
authors.initials: MV
authors.lastname: Bentley
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D005260:Female; D005782:Gels; D018014:Gene Transfer Techniques; D050866:Liquid Crystals / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D050178:Monoglycerides / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*; D014325:Tromethamine / Q000737:chemistry
chemical_list: D000588:Amines; D005782:Gels; D050178:Monoglycerides; D034741:RNA, Small Interfering; D014325:Tromethamine; D019946:Propylene Glycol; C008703:oleylamine
keywords: Gene therapy; In situ gelling; Liquid crystal; Monoglyceride; Oleylamine; siRNA