title: In Situ Gelling Liquid Crystalline System as Local siRNA Delivery System.
abstract: An effective short interfering RNA (siRNA) delivery system protects the siRNA from degradation, facilitates its cellular uptake, and promotes its release into the cytoplasm. Local administration of siRNA presents advantages over systemic administration, such as the possibility to use lower doses and allow local and sustained release. In this context, in situ solidifying organogels based on monoglycerides (MO), polyethylenimine (PEI), propylene glycol (PG) and tris buffer are an attractive strategy for intratumoral delivery of siRNA. In this study, precursor fluid formulation (PFF) composed of MO/PEI/PG/tris buffer at 7.85:0.65:76.5:15 (w/w/w/w) was used to deliver siRNA to tumor cells. The internal structure of the gel obtained from PFF was characterized using small angle X-ray scattering (SAXS). In addition, its ability to complex siRNA, protect it from degradation, and functionally deliver it to tumor cells was investigated. Moreover, in vivo gel formation following intratumoral injection was evaluated. The gel formed in excess water from PFF was found to comprise a mixture of hexagonal and cubic phases. The system was able to complex high amounts of siRNA, protect it from degradation, promote siRNA internalization, and induce gene silencing in vitro in a variety of tumor cell lines. Moreover, a gel formed in situ following intratumoral injection in a murine xenograft model. In conclusion, PFF is a potential delivery system for local and sustained delivery of siRNA to tumor tissue after intratumoral administration.
authors.affiliation: School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo , Avenida do Café, s/n, 14040-903 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Livia N
authors.identifier: 0000-0002-9655-8214
authors.initials: LN
authors.lastname: Borgheti-Cardoso
authors.affiliation: Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht , Heidelberglaan, 100, 3584 CX Utrecht, The Netherlands.|Department of Medical Sciences, The Camussi Laboratory, University of Torino , Via Nizza, 52, 10126 Torino, Italy.
authors.forename: Sander A A
authors.initials: SAA
authors.lastname: Kooijmans
authors.affiliation: Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht , Heidelberglaan, 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Marcel H A M
authors.initials: MHAM
authors.lastname: Fens
authors.affiliation: Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht , Heidelberglaan, 100, 3584 CX Utrecht, The Netherlands.|Department of Biochemistry and Molecular Biology, University of British Columbia , 2350 Health Sciences Mall, Vancouver, British Columbia, Canada , V6T 1Z3.
authors.forename: Roy
authors.initials: R
authors.lastname: van der Meel
authors.affiliation: School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo , Avenida do Café, s/n, 14040-903 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Fabiana T M C
authors.initials: FTMC
authors.lastname: Vicentini
authors.affiliation: Instituto de Física, University of São Paulo , Rua do Matão, 1371, Butantã, 05508-090 São Paulo, São Paulo, Brazil.
authors.forename: Marcia C A
authors.initials: MCA
authors.lastname: Fantini
authors.affiliation: School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo , Avenida do Café, s/n, 14040-903 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Maria Vitória L B
authors.initials: MVLB
authors.lastname: Bentley
authors.affiliation: Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht , Heidelberglaan, 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Schiffelers
mesh_terms: D020868:Gene Silencing / Q000502:physiology*; D050866:Liquid Crystals / Q000737:chemistry*; D050178:Monoglycerides / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D050178:Monoglycerides; D034741:RNA, Small Interfering; D019946:Propylene Glycol; D011094:Polyethyleneimine
keywords: gene silencing; in situ gelling delivery system; liquid crystal; siRNA