Synthesis of Xanthan Gum/Guar Gum/Halloysite nanotubes pH-sensitive hydrogel nanocomposite for controlled release of Quercetin

• A pH-responsive nanocarrier with targeted delivery of quercetin was developed. • The XG/GG/HNTs@QC nanocarrier exhibited a high loading capacity (45.5%) and encapsulation efficiency (84.75%). • The nanocarrier, exhibiting selective behavior toward HepG2 cells, was able to induce apoptosis in them while exerting minimal effects on normal cells, thereby reducing side effects. • The nanocarrier exhibited pronounced pH-responsive behavior by releasing significantly higher amounts of QC in the acidic tumor microenvironment (pH = 5.4) compared to physiological conditions (pH = 7.4). Developing efficient and pH-sensitive drug delivery systems can facilitate the expedited and cost-effective treatment of cancer, a leading global cause of mortality. A nanocarrier composed of xanthan gum, guar gum, and halloysite nanotubes was prepared via a double nanoemulsion approach and applied to achieve sustained and pH-responsive quercetin release. This system can deliver quercetin to the required site in a controlled way. The presence of each component (HNTs, GG, XG) and the interactions between them were confirmed through FT-IR spectroscopy results. The crystalline structure and related characteristics for each component and the nanocarrier were determined by studying and analyzing XRD. The FE-SEM images indicated that the nanocomposite possesses a hydrogel morphology along with an average particle size of 193 nm. The nanocomposite, moreover, exhibited excellent stability, possessing a surface charge of +43 mV. The addition of HNTs led to improved entrapment and loading efficacy for the drugs, from 70.50% to 84.75% and from 36% to 45.5%, in contrast to the system containing no HNT. In addition to that, the addition of the polymers XG and GG enhanced the pH sensitivity for the nanocarrier and the release behavior for quercetin (QC), as in vitro experiment results testified. Furthermore, by the study of various kinetic models, the release kinetics for the drugs were determined. MTT assay revealed the nanocarrier to possess significant cytotoxic activity against the HepG2 cancerous cells. While the in vitro results effectively confirm the therapeutic performance of the nanocarrier, their translation to in vivo conditions, unlike in vitro, where the drug interacts directly with the target cells, is influenced by biological factors such as bioavailability, biodistribution, and route of administration. Overall, considering all the obtained results, the GG/XG/HNTs@QC nanocarrier can act effectively in the tumor tissue environment by responding appropriately to pH. Schematic illustration of the synthesis of XG/GG/HNTs hydrogel nanocomposite loaded with quercetin via the double nanoemulsion method and its therapeutic effects on cancer cells.