Self‐Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma

Abstract

AbstractBackgroundGlioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Paclitaxel (PTX) is a well‐established and highly effective anti‐cancer drug for peripheral solid tumors. However, the application of PTX in GBM is hindered by several limitations, including poor water solubility, restricted entry across the blood–brain barrier (BBB), and enhanced excretion by efflux transporters. P‐glycoprotein (P‐gp) is a crucial efflux transporter that is abundantly present in cerebral vascular endothelial cells and GBM cells. It plays a significant role in the exocytosis of PTX within tumor tissues.MethodsRecently, we have developed a novel technique for creating self‐assembled nanoparticles utilizing a range of natural bioactive molecules. These nanoparticles can encapsulate insoluble drugs and effectively cross the BBB. In additional, we revealed that certain nanoparticles have the potential to act as P‐gp inhibitors, thereby reducing the excretion of PTX. In this study, we conducted a screening of bioactive molecular nanoparticles to identify those that effectively inhibit the function of P‐gp transporters.ResultsAmong the candidates, we identified ursolic acid nanoparticles (UA NPs) as the P‐gp inhibitors. Furthermore, we prepared co‐assembled UA NPs embedded with paclitaxel, referred to as UA‐PTX NPs. Our results demonstrate that UA‐PTX NPs can enhance the blood concentration of PTX, facilitate its entry into the BBB, and inhibit the function of P‐gp, resulting in a decrease in the excretion of PTX. This discovery effectively addressed the above three issues associated with the use of PTX in glioma treatment.ConclusionsUA‐PTX NPs demonstrate strong anti‐tumor effects and show great potential for treating GBM.