Eudragit S 100 Assisted Molecular Solid Dispersion of Andrographolide Tendered Augmented Drug Delivery and Apoptosis in Human Colon Cancer, HT-29 Cells

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-mu g.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 similar to 5.90 and similar to 7.14-fold augmentations in solubility at pH similar to 6.8 and similar to 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 H-1-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 similar to 4.70- and similar to 2.94-fold enhancement in dissolution profile in simulated intestinal fluid (SIF, pH similar to 6.8) and simulated colonic fluid (SCF,pH similar to 7.4) of EUSD4 suggested amendment in the hydrophilicity, wettability properties, and dissolution rate. Furthermore, the IC50 of EUSD4 was similar to 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 (Delta Psi m), 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.