In-vitro investigation of efficacy and toxicity of paclitaxel upon its co-incorporation with natural anti-oxidants to nano-micelles

Chemotherapeutic agents used in chemotherapy treatment not only affect cancer tumors, but also can cause toxic effects in healthy areas. These substances show side effects from time to time due to their oxidation effect. From this point of view, it is sometimes recommended that patients consume antioxidant natural products during chemotherapy in cancer treatment. However, these antioxidant substances may reduce the oxidation effect of the chemotherapy agent at the cancer tumor site and prevent the chemotherapy agent from acting fully. This issue should be clarified. From this point, the antioxidant effect of curcumin, quercetin and rosmarinic acid compounds were applied to cancer cells together with chemotherapy agent paclitaxel and the effect of this agent was investigated. For this purpose, the natural antioxidants compounds were loaded into nano-carriers and the effect of paclitaxel on breast cancer cells was investigated. The reason for the loading of natural antioxidants in the nano-carrier is that these substances can be applied to the cells at a high rate by removing their low solubility property in water. To this end, poly lactide co-glycolide (PLGA) nano-micelles were used. The water-soluble commercial form of Paclitaxel was applied to the cells. The nano-formulation of each antioxidant was prepared separately using the o/w method. Briefly, the antioxidant and PLGA were dissolved together in acetone and slowly dropped into water containing the surfactant. The organic solvent was removed at room temperature by stirring overnight. The size of the nanofomulations obtained were determined by Dynamic Light Scattering (DLS) method. The antioxidants were loaded into the nao-carrier with increasing concentrations, and the highest concentration with no aggregate, ie the formulation in which the entire compound was loaded into the micelle, was considered as the optimized formulation. The concentration of paclitaxel equal to the IC 50 value was applied to MCF-7 human breast cancer cells with various concentrations of nano-antioxidants and changes in cell viability were observed. Cell viability was measured by Sulforhodamine B assay. In addition, nano-anti-oxidant was applied to the cells together with paclitaxel, 1 hour before paclitaxel and 1 hour after paclitaxel, and the effect of time of administration on the results was investigated. In conclusion, it was observed that curcumin significantly reduced the anti-tumor effect of Paclitaxel. Quercetin reduced the anti-tumor effect of paclitaxel in a dose-dependent manner. There was no significant effect of rosmarinic acid. It was observed that the application time had no function on the change of these effects. Ultimately, the bioavailability of antioxidant and its concentration in the blood will remain unknown unless the concentration of the antioxidant in the blood circulation is known. This will cause the unknown direction of the natural antioxidant on affecting the effect of chemotherapy on the tumor site. From this it can be clearly concluded that antioxidants should not be used during cancer treatment unless the xiv effect of the anti-oxidant on the chemotherapy agent and ultimately its negative impact on the growth of the cancer tumor is fully understood