Novel design of quercetin nanosuspension for enhanced biopharmaceutical performance

This study describes how quercetin nanosuspensions (QCT NS) were developed using co- crystallization with isonicotinamide or theobromine in order to improve the solubility and bioavailability of quercetin, an antioxidant, antiinflammatory, and anticancer agent for the treatment of Chronic Myeloid Leukemia (CML). Co-crystallization methods were characterized by FTIR analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), proving the effectiveness of this method to prepare QCT NS without any residual contaminants. Isonicotinamide at a molar ratio of 1:1.5 was the most effective co-former with the highest drug content (100.1%) and smallest particle size, whereas theobromine (ratio of 1:2) provided the best in vitro dissolution, with cumulative release of QCT in the first 8 hours greater than pure quercetin, attributed to improved surface area and reduced crystallinity. In vitro anticancer studies performed on K562 CML cells using the MTT assay indicated a dose-dependent cytotoxic effect of QCT NS, with viability decreasing from 86% at 10 µg/mL to 15% at 100 µg/mL (with an IC50 of 55.8 µg/mL). Apoptosis evaluations employing acridine orange staining, 76% cytotoxicity based on the LDH assay, and neutral red uptake (viability decreased to 31% at 100 µg/mL) were supportive of the improved therapeutic aspect and emphasized the benefits of utilizing co-crystal nanosuspension in improving QCT clinical impact in the management ofCML.