An innovative synergistic combination using eudragit-coated galactosylated PLGA-pluronic nanoparticles for addressing colorectal cancer

Abstract

The goal of this research was to find a way to enhance the pharmacological activity of Capecitabine (CAP) and Thymoquinone (TQ) while also decreasing the likelihood of drug resistance by studying the synergistic activity of TQ, formulating the functionalized polymeric nanoparticles (PNPs) as carriers for effectively targeting the colon to manage colorectal cancer (CRC). CAP and TQ-loaded galactosylated PLGA nanoparticles coated with Eudragit-S-100 were created and optimized to target the colon's pH for drug release after oral delivery using Box-Behnken design. The standard study revealed that they had a high stability of normal pH, a tiny size of spherical shape droplets, and a unique zeta potential that was non-toxic and promoted faster cell migration. Cancer cells treated with PNPs that had a protective effect on intracellular reactive oxygen species (ROS), oxidative stress, and mitochondrial membrane potential had their apoptotic morphology altered to promote cell survival. Moreover, the investigation of pharmacodynamics on male Wistar rats unveiled a notable reduction in the number of tumors, aberrant crypt foci, accompanied by a discernible amelioration in dysplastic characteristics and enhancement in various blood parameters, and its toxic effects were mitigated proving Galactosylation to be a reliable method which has shown to be useful in targeting CRC through galectin-mediated endocytosis. When compared to free CAP, the targeted approach increases cytotoxicity and cell death. The data demonstrated that the targeted method maximized the efficacy of CAP in regulating tumor development, enhancing apoptosis and decreasing drug resistance. This demonstrated that the engineered PNP showed encouraging anticancer activity with less toxicity and may be employed as an efficient carrier against cancer. Docking research stated that TQ had the maximum binding affinity to Mitogen-activated protein kinase kinase molecule which is inextricably linked to colon cancer (binding energy −6.07 kcal/mol). This is the first work to our knowledge to demonstrate that eudragit S-100 coated CAP and TQ-loaded Galactosylated PLGANP can induce apoptosis, which could be used to kill off cancer cells.