Improved synergistic anticancer action of quercetin and tamoxifen citrate supported by an electrospun complex nanostructure

[Display omitted] •Tri-chamber nanofibers in the form of core–shell microstructure embedded on one side of the Janus main structure were designed.•Hydrophilic and pH sensitive polymers were combined skillfully in complicated structure nanocomposites.•The tri-chamber nanofibers facilitated the rapid release of quercetin and the delayed and sustained release of tamoxifen citrate.•The tri-chamber nanofibers could result in a synergistic anticancer action of quercetin and tamoxifen citrate. A tri-fluid electrospinning process was successfully developed to prepare tri-chamber complex nanofibers. The core–shell and Janus structure were combined to form a delicate and complicated architecture for solving the problem of co-administration of quercetin and tamoxifen citrate, improving the oral bioavailability, and enhancing their synergistic anti-breast cancer actions. Scanning electron microscope, transmission electron microscope and confocal fluorescent microscopy images showed the complex structure of the designed nanofibers. Fourier transform infrared and X-ray diffraction analyses verified that the model drugs and the polymeric excipients had good compatibility and were presented in an amorphous state. The in vitro release study certified that the tri-chamber nanofibers facilitated the rapid release of quercetin compared with that of the crude drug (90% versus 38%) and the delayed and sustained release of tamoxifen citrate at the same time interval (decreased by 1.88 times). The in vivo pharmacokinetic and pharmacodynamic analysis verified that the tri-chamber nanofibers could result in increased oral bioavailability and enhanced synergistic anticancer action of quercetin and tamoxifen citrate. The findings proved that a new medicated drug delivery system with advanced dual-, time-, and target-specific drug release profiles was developed using the electrospun complex nanostructure.