In Situ Gelling Liquid Crystalline System as Local siRNA Delivery System

Autor(es)

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.

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR PHARMACEUTICS; v. 14, n. 5, p. 1681-1690, MAY 2017.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 04/09465-7 - Laboratório multiusuário de caracterização de sistemas de liberação micro - e nanodispersos de fármacos
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 13/02132-1 - Avaliação in vivo de sistema de geleificação in situ no tratamento do carcinoma de células escamosas após administração intratumoral
• Beneficiário: Lívia Neves Borgheti Cardoso
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado