Synergistic effects of curcumin and piperine in cocrystal form: a breakthrough in bladder cancer therapy

Curcumin (CUR) is a promising anticancer agent for urinary bladder cancer (UBC) but is hindered by poor oral bioavailability. This study investigates the role of cocrystal technology in overcoming these limitations through the formation of curcumin-piperine (CUR-PIP) cocrystals (CoCry). The CUR-PIP CoCry was evaluated for its ability to suppress IGF2 over expression in UBC. Molecular interactions were predicted <i>via</i> Auto Dock simulations, and the co crystals were characterized using FTIR, DSC, PXRD, SEM, and ssNMR. Saturation solubility, dissolution, permeability, and <i>in vivo</i> pharmacokinetic studies were conducted. The therapeutic efficacy of CUR-PIP CoCry was tested in a bladder cancer rat model induced by N-Methyl Nitrosourea; with IGF2 expression quantified using qRT-PCR and flow cytometry. The CUR-PIP CoCry demonstrated enhanced drug release and permeability compared to CUR alone. Pharmacokinetic analysis revealed a 5.7-fold increase in C_max and a 7.9-fold increase in AUC_{0-12 hr} compared to CUR alone. <i>In vivo</i> studies using an MNU-induced bladder cancer rat model demonstrated that CUR-PIP CoCry significantly suppressed IGF2 expression (<i>p</i> < 0.001) and enhanced anticancer efficacy. This study underscores the potential of cocrystallization as a novel approach to enhance bioavailability and therapeutic effectiveness in cancer treatment.