A novel modified chitosan/collagen coated-gold nanoparticles for 5-fluorouracil delivery: Synthesis, characterization, in vitro drug release studies, anti-inflammatory activity and in vitro cytotoxicity assay

Abstract We report herein the development of the novel nanohybrids of gold nanoparticles reduced/stabilized/ coated with collagen (AuNPs@collagen) in the first layer and subsequently modified with biotin-quat188-chitosan (Bi-QCS) in the outer layer for 5-fluorouracil (5-FU) delivery to improve cellular uptake and promote specific cell targeting of the nanocarrier. The fabrication of the layer-by-layer technique on the surface of gold nanoparticles (AuNPs) can overcome the limitation of poor drug loading capacity of the classic AuNPs from 64.67% to 87.46%. The AuNPs@collagen coated by the Bi-QCS exhibits strong electrostatic interactions between drug anion (5-FU) and amine groups of the modified chitosan as well as hydrogen bonding. Furthermore, the Bi-QCS-AuNPs@collagen demonstrated a significantly higher anti-inflammatory activity in RAW264.7 macrophage cell line. The Bi-QCS-AuNPs@collagen enhanced the activity of 5-FU approximately 3.3-fold (HeLa) and 6.2-fold (A549), compared to the free 5-Fluorouracil. According to these results, it is very promising that Bi-QCS-AuNPs@collagen can be used as an effective drug delivery carrier in the future.