RESUMEN

The study shows that RADA-F6 peptide with pH-responsive self-assembling nature can be effectively used as a drug delivery system for the sustained release of a potent anticancer drug 5-fluorouracil (5-FU) at basic pH. As 5-FU contains the aromatic pyrimidine ring, RADA-F6 system is suitable for entrapping an aromatic drug due to effective π-π stacking with phenylalanine and be able to show better controlled release behavior. The stability and controlled release nature of RADA-F6 in different conditions followed by 5-FU entrapment at in silico conditions was confirmed by molecular dynamics simulation taking RADA-16 as control. Cytotoxicity of the drug-loaded RADA-F6 was measured by MTT assay and cellular uptake by confocal microscopy. Physicochemical characterization and further Western blot analysis and flow cytometric studies confirm that RADA-F6 can be successfully used as an efficient vector for pH-sensitive, controlled 5-FU delivery system.

Asunto(s)

Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Fluorouracilo/administración & dosificación , Nanofibras/química , Fenilalanina/química , Antimetabolitos Antineoplásicos/administración & dosificación , Apoptosis , Dicroismo Circular , Sistemas de Liberación de Medicamentos , Células HCT116 , Humanos , Hidrogeles/química , Concentración de Iones de Hidrógeno , Cinética , Microscopía Confocal , Microscopía Electrónica de Transmisión , Simulación de Dinámica Molecular , Nanomedicina/métodos , Péptidos/química , Espectrometría de Fluorescencia