Self-assembling peptide nanofibers containing phenylalanine for the controlled release of 5-fluorouracil

Int J Nanomedicine. 2016 Oct 25:11:5583-5594. doi: 10.2147/IJN.S104707. eCollection 2016.

Abstract

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.

Keywords: aromatic; drug delivery; nanofibrous; scaffold.

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage
  • Apoptosis
  • Circular Dichroism
  • Delayed-Action Preparations / chemistry*
  • Drug Carriers / chemistry*
  • Drug Delivery Systems
  • Fluorouracil / administration & dosage*
  • HCT116 Cells
  • Humans
  • Hydrogels / chemistry
  • Hydrogen-Ion Concentration
  • Kinetics
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Molecular Dynamics Simulation
  • Nanofibers / chemistry*
  • Nanomedicine / methods
  • Peptides / chemistry
  • Phenylalanine / chemistry*
  • Spectrometry, Fluorescence

Substances

  • Antimetabolites, Antineoplastic
  • Delayed-Action Preparations
  • Drug Carriers
  • Hydrogels
  • Peptides
  • Phenylalanine
  • Fluorouracil