Given that basal levels of reactive oxygen species (ROS) are higher in cancer cells, there is a growing school of thought that endorses pro-oxidants as potential chemotherapeutic agents. Intriguingly, cerium oxide (CeO2) nanoparticles can manifest either anti- or pro-oxidant activity as a function of differential pH of various subcellular localizations. In an acidic pH environment, for example, in extracellular milieu of cancer cells, CeO2 would function as a pro-oxidant. Based on this concept, the present study is designed to investigate the pro-oxidant activities of CeO2 in human colorectal carcinoma cell line (HCT 116). For comparison, we have also studied the effect of ceria nanoparticles on human embryonic kidney (HEK 293) cells. Dose-dependent viability of cancerous as well as normal cells has been assessed by treating them independently with CeO2 nanoparticles of different concentrations (5–100 μg/mL) in the culture media. The half maximal inhibitory concentration (IC50) of nanoceria for HCT 116 is found to be 50.48 μg/mL while that for the HEK 293 cell line is 92.03 μg/mL. To understand the intricate molecular mechanisms of CeO2-induced cellular apoptosis, a series of experiments have been conducted. The apoptosis-inducing ability of nanoceria has been investigated by Annexin V-FITC staining, caspase 3/9 analysis, cytochrome c release, intracellular ROS analysis, and mitochondrial membrane potential analysis using flow cytometry. Experimental data suggest that CeO2 treatment causes DNA fragmentation through enhanced generation of ROS, which ultimately leads to cellular apoptosis through the p53-dependent mitochondrial signaling pathway.
Objective: The objective of this study was to encapsulate ibuprofen in microspheres made of Eudragit® RL100 as the polymer and evaluate it in vitro. Methods: Microspheres were prepared by the solvent evaporation method. Significant parameters in the evaluation of microencapsulation are yield, particle size, encapsulation efficiency, swelling index, uniformity factor and buoyancy. The in vitro release studies were carried out in phosphate buffer solution pH 7.4 at 37±1 ᵒC. Results: Microspheres containing higher ratio of polymer had higher yields as high as 89.25%. The external diameter ranged from 300 to 550 μ, with geometric mean close to 420 μ. Evidently, the formulation containing higher concentration of Eudragit® RL100 had a larger diameter, indicating greater cross-linking and a larger sphere, signifying a higher loading capacity. The loading efficiency was above 81%, while the swelling index was found to be between 29% to 36%, with buoyancy factor of 74.53% for the superior batch. The results suggest that ibuprofen was successfully and efficiently encapsulated. The release rates of drug-loaded microspheres are related to the amount of polymer, thus, to get extended drug release while reducing the ill effects of the drug in the stomach. In vitro release was compared with marketed product, divulging better data for the indigenously prepared samples. Conclusion: Data obtained by matching the in vitro release for the superior microspheres, so prepared and one of the commercial products showed the indigenous preparation of ibuprofen microspheres to be a better performer in the simulated gastric environment of phosphate buffer solution pH 7.4 at 37±1 ᵒC.