Chitosan-quercetin complex containing nanospheres for targeted delivery of methotrexate against MCF-7 breast cancer cells.

Present study aimed to enhance anticancer effect of methotrexate (MTX) by incorporating it into Chitosan-Quercetin complex (CH-Qt) nanospheres specifically targeting breast cancer MCF-7 cell lines with improved anti-inflammatory effect. Three formulations optimized by Box Behnken design (BBD) i.e., chitosan-polycaprolactone (CH-PCL-Ns), quercetin-polycaprolactone (Qt-PCL-Ns) and chitosan-quercetin-polycaprolactone (CH-Qt-PCL-Ns) were prepared and after MTX loading, characterized by polydispersity index (PDI), particle size, zeta potential, surface morphology, in-vitro drug release, mucoadhesion, membrane permeability. In-silico molecular docking studies were conducted to assess binding interactions of CH-Qt complex with high mobility group protein B1 (HMG-1). The CH-Qt-PCL-MTX-Ns showed reduced edema upto14% in rat paw till 4 h, drug release by CS-QT-PCL-MTX-Ns was 50.4 ± 2.5% in sustained manner, while CS-PCL-MTX-Ns showed the highest value of mucoadhesion 40 ± 1.25%. The lowest MAD value was shown by CS-QT-PCL-MTX-Ns, which was 135.59 μg and 180.78 μg per 0.636cm2. Docking analysis revealed higher binding interaction of CH-Qt complex as compared to quercetin on amino acid residues of targeted protein. CS-QT-PCL-MTX-Ns at a concentration of 120 μg/mL at 72 h which was 14 ± 2.0% exhibited dose dependent cytotoxicity against MCF-7 breast cancer cells with PDI < 0.5. Conclusively, CH-Qt-PCL-MTX-Ns demonstrate promising potential for the management of breast cancer along with enhanced anti-inflammatory effect.