Publication

Abstract : Colorectal cancer is the second most common cause of death due to growing incidence. Andrographolide (AGD) induces apoptosis in colorectal cancer cells; however, oral administration of AGD is associated with hindered aqueous solubility (3.29 ± 0.73-μg.mL−1) and bioavailability of 15.87 ± 3.84%. Therefore, in the current investigation, AGD was amalgamated with Eudragit S100 (EUS100) to engineer a molecular amorphous solid dispersion (EUSD). EUSD4, an optimized molecular solid dispersion showed ~ 5.90 and ~ 7.14-fold augmentations in solubility at pH ~ 6.8 and ~ 7.4, respectively as compared to AGD alone. The% assay and drug loading were respectively measured to be 96.01 ± 3.52% and 19.85 ± 0.65%. ATR and 1H-NMR spectroscopies confirmed that the -OH group of AGD formed an intermolecular hydrogen bond with the –C = O of EUS100. Moreover, a hallo pattern of PXRD, the disappearing of an endothermic peak in DSC, the absence of a birefringence pattern under polarized light, and disorders in the initial particle shape confirmed the amorphous state of EUSD4. In addition, a ~ 4.70- and ~ 2.94-fold enhancement in dissolution profile in simulated intestinal fluid (SIF, pH ~ 6.8) and simulated colonic fluid (SCF,pH ~ 7.4) of EUSD4 suggested amendment in the hydrophilicity, wettability properties, and dissolution rate. Furthermore, the IC50 of EUSD4 was ~ 1.42-fold higher than AGD, indicating improvement in anticancer efficacy against HT-29 cells. EUSD4 exhibited superior cytotoxicity over AGD owing to the induction of apoptotic cell death, mitochondrial membrane loss (ΔΨm), remarkable S-G2/M phase cell-cycle arrest and enhanced ROS generation in HT-29 cells. In conclusion, EUSD4 warrants further in-vivo antitumor testing under a set of stringent parameters against colorectal cancer.