Eudragit S 100 Assisted Molecular Solid Dispersion of Andrographolide Tendered Augmented Drug Delivery and Apoptosis...

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-microg.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.