Development of chitosan/halloysite/graphitic‑carbon nitride nanovehicle for targeted delivery of quercetin to enhance its limitation in cancer therapy: An in vitro cytotoxicity against MCF-7 cells

Abstract

Although quercetin (QC) has valuable advantages, its low water solubility and poor permeability have limited its utilization as an anticancer drug. In this study, hydrogel nanocomposite of chitosan (CS), halloysite (HNT), and graphitic‑carbon nitride (g-C3N4) was prepared and loaded by QC using a water in oil in water emulsification process to attain QC sustained-release. Using g-C3N4 in the HNT/CS hydrogel solution enhanced the entrapment effectiveness (EE %) by up to 86 %. The interactions between QC and nanoparticles caused the nanocomposite pH-responsive behavior that assists in minimizing the side effect of the anticancer agent by controlling the burst release of QC at neutral conditions. According to DLS analysis, the size of the QC-loaded nanovehicle was 454.65 nm, showing that nanoparticles are highly monodispersed, which also was approved by FE-SEM. Additionally, Zeta potential value for the fabricated drug-loaded nanocarrier is +55.23 mV displaying that nanoparticles have good stability. The hydrogel nanocomposite structure's completeness was shown by FTIR pattern, and quercetin was included into the designed delivery system based on XRD data. Besides, the drug release profile indicated that a targeted sustained-release and pH-sensitive release of anticancer drug with the 96-hour extended-release were noticed. In order to comprehend the process of QC release at pH 5.4 and 7.4, four kinetic models were employed to find the best-suited model according to the acquired release data. Finally, the MTT experiment revealed considerable cytotoxicity against breast cancer cells, MCF-7 cell line was experimented in vitro, for the CS/HNT/g-C3N4 targeted delivery system in comparison to QC as a free drug. According to the above description, the CS/HNT/g-C3N4 delivery platform is a unique pH-sensitive drug delivery system for anticancer purposes that improves loading as well as sustained-release of quercetin.