Enhancing the anti-cancer potential of resveratrol through cocrystal technology in colorectal cancerous rats

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide, and the limitations of current chemotherapeutic regimens necessitate alternative therapeutic approaches. Resveratrol (RES) possesses potent anticancer activity but suffers from poor solubility and low bioavailability. In this study, cocrystallization with quercetin (QUE) was employed as a strategy to overcome these limitations and enhance the therapeutic performance of RES. Resveratrol-Quercetin cocrystals (RES-QUE CoCry) were prepared by the solvent evaporation method to enhance physicochemical and pharmacokinetic properties. The cocrystals exhibited a novel crystalline phase with a 2-fold increase in solubility at pH 6.8 and a 2.64 fold increase in permeability compared to pure RES. Pharmacokinetic analysis showed a 3.2fold increase in C_max and a 3.5fold rise in AUC_{0-24 h}, confirming enhanced bioavailability. In N-methyl-N-nitrosourea (MNU) induced CRC rat model, RES-QUE CoCry treatment restored epithelial integrity, reduced inflammation. qRTPCR and western blot analysis showed down regulated BCL2 expression, indicating potentiated pro-apoptotic activity. By this study, it was proved that cocrystallization of RES with QUE enhances both bioavailability and in-vivo anticancer efficacy, offering a novel phytochemical-based strategy for CRC management.