Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity

Abstract

Mitoxantrone (MIT) is a chemotherapeutic agent with promising anticancer efficacy. In this study, Pluronic F68-vitamine E succinate (F68-VES) amphiphilic polymer micelles were developed for delivering MIT and enhancing its anticancer activity. MIT-loaded F68–VES (F68–VES/MIT) micelles were prepared via the solvent evaporation method with self-assembly under aqueous conditions. F68–VES/MIT micelles were found to be of optimal particle size with the narrow size distribution. Transmission electron microscopy images of F68–VES/MIT micelles showed homogeneous spherical shapes and smooth surfaces. F68–VES micelles had a low critical micelle concentration value of 3.311 mg/L, as well as high encapsulation efficiency and drug loading. Moreover, F68–VES/MIT micelles were stable in the presence of fetal bovine serum for 24 hours and maintained sustained drug release in vitro. Remarkably, the half maximal inhibitory concentration (IC 50 ) value of F68–VES/MIT micelles was lower than that of free MIT in both MDA-MB-231 and MCF-7 cells (two human breast cancer cell lines). In addition, compared with free MIT, there was an increased trend of apoptosis and cellular uptake of F68–VES/MIT micelles in MDA-MB-231 cells. Taken together, these results indicated that F68–VES polymer micelles were able to effectively deliver MIT and largely improve its potency in cancer therapy.

Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin E succinate conjugates for improved lung cancer treatment

“…Therefore, due to its hydrophobicity and synergistic therapeutic effects, VES is considered to be a promising agent in drug delivery systems 14 and thereby is frequently modified as nanocarriers to deliver anticancer drugs. For instance, chitosan-vitamin E succinate copolymer (CS-VES), 15 polyethylene glycol-derivatized vitamin E copolymer, 16 and vitamin E succinate-conjugated F68 micelles 17 have all been synthesized and exhibited a high drug loading (DL) capacity. Unfortunately, the hydrophobic interactions between the encapsulated drug and hydrophobic VES of these nanoparticles led to a problematic slow release.…”

Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer

“…In this study, DSPE-PEG 2000 was selected as a starting material considering that it is an amphiphilic copolymer and can be self-assembled into uniform micelles with small sizes. 27 Another starting material, TPGS 1000 , was used together with DSPE-PEG 2000 to endue the resulting micelles with a new ability to inhibit the functions of P-gp and, in turn, to overcome the MDR of certain cancer cells.…”

“…Another component in PMs, namely, TPGS 1000 , is one of the membrane efflux transporters and has inhibiting functions against the adenosine triphosphate (ATP)-dependent pump P-glycoprotein (P-gp). [27][28][29] In addition to its application in enhanced chemotherapy, TPGS has recently been used as a component to modify solid-lipid nanoparticles for overcoming P-gp-mediated MDR related to leukemia. 30 In these applications, TPGS 1000 has shown certain ability to inhibit the exocytosis of the internalized nanoparticles from cancer cells.…”

“…30 In these applications, TPGS 1000 has shown certain ability to inhibit the exocytosis of the internalized nanoparticles from cancer cells. [27][28][29][30] Therefore, it would be possible to help DOX to circumvent the MDRassociated pathways in some cancer cells while enhancing the anticancer efficacy of DOX if the carriers used for the delivery of DOX could be built using DSPE-PEG 2000 and TPGS 1000 .…”

“…36,37 Therefore, in contrast to DOX alone, the stronger inhibitory effect of DOX + CUR on the growth of A549/Adr cells can be attributed to the synergistic actions of DOX + CUR. In the case of (DOX + CUR)-PMs, the component TPGS 1000 present in the micelles has inhibiting functions against P-gp, 27,31 and on the other hand, micelles could help to transfer more CUR molecules into A549/Adr due to the protection functions of micelles. Therefore, the actions of DOX, CUR, and TPGS 1000 synergistically enable (DOX + CUR)-PMs to have much higher cytotoxicity toward A549/Adr cells in comparison to the simple combination of DOX and CUR.…”