In Situ Gelling Liquid Crystalline System as Local siRNA Delivery System
| Autor: | Fabiana T. M. C. Vicentini, Márcia Carvalho de Abreu Fantini, Roy van der Meel, Maria Vitória Lopes Badra Bentley, Sander A.A. Kooijmans, Raymond M. Schiffelers, Marcel H.A.M. Fens, Lívia Neves Borgheti-Cardoso |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Tris Small interfering RNA Pharmaceutical Science Context (language use) 02 engineering and technology 03 medical and health sciences chemistry.chemical_compound gene silencing In vivo Drug Discovery Journal Article Polyethyleneimine Gene silencing in situ gelling delivery system liquid crystal RNA Small Interfering Polyethylenimine Chemistry BIOTECNOLOGIA 021001 nanoscience & nanotechnology Propylene Glycol Molecular biology In vitro Liquid Crystals 030104 developmental biology siRNA Biophysics Systemic administration Monoglycerides Molecular Medicine 0210 nano-technology |
| Zdroj: | Molecular pharmaceutics, 14(5), 1681. American Chemical Society Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1543-8384 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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