Preparation and characterization of quercetin-loaded folic acid TPGS micelles against MCF-7 breast cancer cell line

Abstract

Breast cancer is one of the common cancers in the world and possibility of this disease among women is higher. In recent years, variety of nanoparticles have been discovered and synthesized in such a way to increase the therapeutic efficiency of drugs through targeted area of tumor cells without causing any harm towards healthy tissues. Quercetin is a polyphenolic compound that exists in plants, fruits, and vegetables and has showed numerous promising health benefits. However, therapeutic applications of quercetin are limited due to its low water solubility and poor bioavailability. The main objectives of this study were to synthesize quercetin loaded folic acid d-α-tocopheryl polyethylene glycol succinate (TPGS) polymeric micelles (QUE-FA-TPGS-PMs), to characterize the physicochemical properties of QUE-FA-TPGS-PMs and to analyze the in vitro cytotoxicity of QUE-FA-TPGS-PMs against MCF-7 breast cancer cells. The TPGS micelles containing quercetin were prepared by thin film hydration method and were characterized for their particle size, polydispersity (PDI), encapsulation efficiency (EE), drug loading (DL), critical micelle concentration (CMC), in vitro drug release, and in vitro cytotoxicity. Particle size and polydispersity were analyzed using a zetasizer while surface morphology was determined by transmission electron microscopy (TEM). The EE and DL were determined by ultraviolet-visible (UV-Vis) spectrophotometry while the in vitro drug release studies of micelles were carried out by dialysis bag diffusion method. The in vitro cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay where the cell viability was measured after 24, 48 and 72 h of incubations. It was observed that the average size of both QUE-FA-TPGS-PMs were between 118.53 nm and 651.55 nm. This indicates that these PMs can escape reticuloendothelial system (RES) and have longer circulation in blood. The PDI values were recorded between 0.23 and 0.67 revealed that these PMs were stable. From the TEM results, it can be observed that the QUE-FA-TPGSPMs were in a spherical shape. The QUE-FA-TPGS-10.0 displayed high EE of 99.80% with low CMC of 0.008%. The lower value of CMC indicates greater stability upon dilution. After 96 h, drug release from the QUE-FA-TPGS-10.0 reached 39.42% maximum cumulative percentage of quercetin release. This slower release of quercetin indicates the QUE-FA-TPGS-10.0 was able to be sustainably released. The QUE-FA-TPGS-10.0-PMs exhibited the lowest cell viability of 23.6% against MCF-7 cells after 72 h of incubation. From the findings, it can be concluded that quercetin was successfully loaded inside PMs. These QUE-FA-TPGS-PMs were able to specifically target MCF-7 cells, delivered quercetin inside MCF-7 cells and cause cytotoxicity, thus can supports their role as a new targeted drug delivery system against MCF-7 breast cancer cells.