Micelles of d-α-Tocopheryl Polyethylene Glycol 2000 Succinate (TPGS 2K) for Doxorubicin Delivery with Reversal of Multidrug Resistance

Abstract

The purpose of this study is to investigate the ability of doxorubicin (DOX)-loaded d-α-tocopheryl polyethylene glycol 2000 succinate (TPGS 2K) micelles to overcome MDR in breast cancer treatment. The DOX-loaded TPGS 2K micelles exhibited an average size of around 23 nm, a near neutral zeta potential of around 4 mv and high encapsulation efficiency (85.22 ± 1.89%). The TPGS 2K conjugate did not have significant influences on the reduction of mitochondrial membrane potential (MMP) and the depletion of intracellular ATP level of MCF-7/ADR cells but had an evident effect on the inhibition of Verapamil-induced P-gp ATPase activity. In vitro cell culture experiments demonstrated the DOX-loaded TPGS 2K micelles, resulting in higher cellular uptake and more significant cytotoxicity effect against MCF-7/MDR cells than the free DOX solution. Additionally, the in vivo imaging study revealed DiR-loaded TPGS 2K micelles distributed selectively in MCF-7/ADR tumor-bearing nude mice and had a sufficient residence time. In the anticancer efficacy test with MCF-7/ADR tumor bearing nude mice, the DOX-loaded TPGS 2K micelles displayed significantly higher antitumor activity compared with free DOX solution at the same DOX dosage but less toxicity evaluated by the change of body weight and histological examination. Therefore, this drug delivery micellar system based on TPGS 2K conjugates can serve as a potential nanomedicine for reversing MDR.

Non-Lamellar Liquid Crystalline Nanocarriers for Thymoquinone Encapsulation

“…Notably, increasing TPGS-PEG2000 concentration at both lipid compositions, particularly at GMO/Vit E ratio of 60:40 ( Figure 2B), did not have a significant influence on the lattice parameters of both coexisting H 2 and cubic Fd3m phases ( Table 1). This is most likely attributed to the tendency of TPGS-PEG2000 to form micelles and vesicles as previously reported [48,49]. At GMO/Vit E ratio of 70:30 (Figure 2A), the results showed a slight increase in the lattice parameter of the coexisting H 2 phase on increasing TPGS-PEG2000 concentration from 0.75 to 1.5 wt%.…”

“…These small aggregates are most likely representing coexisting vesicles. Considering the tendency of TPGS-PEG2000 to form normal micelles (L 1 phase) [48,49], we do not exclude the coexistence of micelles in these nanodispersions. In addition to these, other relatively larger deformed and elongated vesicular structures (marked with black dash arrows) were also visible in cryo-TEM images (Figure 3).…”

P-gp Inhibition and Mitochondrial Impairment by Dual-Functional Nanostructure Based on Vitamin E Derivatives To Overcome Multidrug Resistance

“…The final product TPGS 2k was obtained after lyophilization, as a white powder. 17,18 The product was analyzed using proton nuclear magnetic resonance 1 H NMR (AVANCE III, Bruker BioSpin, Germany) in CDCl 3 and Fourier transform infrared (FTIR) spectroscopies (Spectrum One, PerkinElmer Instruments Co., Ltd., USA) in the range of 4000–400 cm −1 .…”

Co-delivery of hydrophilic gemcitabine and hydrophobic paclitaxel into novel polymeric micelles for cancer treatment

“…The FTIR analysis of the spectrums for FA, PEG-VE was reported. 24,25 The FT-IR spectrum is shown in Synthesis of GEM-VE. The synthetic route of GEM-VE is shown in Fig.…”