Enhancing doxorubicin efficacy with vitamin E-TPGS nanosystems in cancer therapy

Abstract

Doxorubicin, a commonly used chemotherapeutic medication, poses substantial hurdles due to the development of resistance in tumor cells. Resistance mechanisms include up-regulation of efflux pumps such as P-gp, improved drug metabolism, and evasion of apoptosis. P-gp is an important membrane-bound efflux pump involved in multidrug resistance in cancer cells. It decreases the intracellular concentration and efficiency of many medicines, including chemotherapeutics like doxorubicin, by actively moving them out of cells. The MDR1 gene encodes this protein, which is highly expressed in a variety of organs, including the liver, kidney, and intestines, as well as many cancers. Inhibiting P-gp activity is a critical method for combating drug resistance and improving chemotherapeutic effectiveness. Due to this, novel approaches are being investigated, such as adding TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate) to therapeutic formulations, which can block efflux pumps and improve drug solubility and bioavailability. TPGS is a water-soluble vitamin E derivative that functions well as an enhancer of drug delivery and because of its amphiphilic nature, it can function as a surfactant which enhances the solubility and bioavailability of poorly soluble medications. Another well-known property of TPGS is its capacity to inhibit P-glycoprotein (P-gp), which allows cancer cells to withstand drugs and overcome drug efflux. Because of this, TPGS is a useful ingredient in the formulation of chemotherapy drugs like doxorubicin by improving their therapeutic effectiveness. The potential of TPGS in overcoming the resistance of doxorubicin was discussed in this review article.