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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

In Situ Gelling Liquid Crystalline System as Local siRNA Delivery System

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Author(s):
Borgheti-Cardoso, Livia N. ; Kooijmans, Sander A. A. ; Fens, Marcel H. A. M. ; van der Meel, Roy ; Vicentini, Fabiana T. M. C. ; Fantini, Marcia C. A. ; Bentley, Maria Vitoria L. B. ; Schiffelers, Raymond M.
Total Authors: 8
Document type: Journal article
Source: MOLECULAR PHARMACEUTICS; v. 14, n. 5, p. 1681-1690, MAY 2017.
Web of Science Citations: 3
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 sytemic 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 7.85:0.65:763:15 (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. (AU)

FAPESP's process: 13/02132-1 - In vivo evaluation of in situ gelling systems to treatment of squamous cell carcinoma after intratumoral administration
Grantee:Lívia Neves Borgheti Cardoso
Support Opportunities: Scholarships abroad - Research Internship - Doctorate