Vitamin E D-alpha-tocopheryl polyethylene glycol 1000 succinate-conjugated liposomal docetaxel reverses multidrug resistance in breast cancer cells

Abstract

Objectives Multidrug resistance (MDR) remains a primary challenge in breast cancer treatment. In the present study, D‐alpha‐tocopheryl polyethylene glycol 1000 succinate (TPGS)‐coated docetaxel‐loaded liposomes were developed as a novel drug delivery system to reverse MDR and enhance breast cancer therapy compared with the traditional liposomes, DSPE‐mPEG‐coated liposomes (stealth liposomes) and commercial Taxotere®. Key findings Liposomes were prepared by thin – film dispersion method. Evaluations were performed using human breast cancer MCF‐7 and resistant MCF‐7/ADR cells. The reversal multidrug‐resistant effect was assessed by P‐gp inhibition assay, cytotoxicity, cellular uptake and apoptosis assay. Results The TPGS‐chol‐liposomes were of an appropriate particle size (140.0 ± 6.0 nm), zeta potential (−0.196 ± 0.08 mv), high encapsulation efficiency (99.0 ± 0.9) and favourable in vitro sustained release. The TPGS‐coated liposomes significantly improved cytotoxicity and increased the intracellular accumulation of docetaxel in both types of breast cancer cells. The TPGS‐coated liposomes were confirmed to induce apoptosis via a synergistic effect between docetaxel and TPGS. It was demonstrated that TPGS enhanced the intracellular accumulation of drug by inhibiting overexpressed P‐glycoprotein. Conclusions The TPGS‐conjugated liposomes showed significant advantages in vitro compared with the PEG‐conjugated liposomes. The TPGS‐conjugated liposomes could reverse the MDR and enhance breast cancer therapy.

Inhibition of Chemoresistance in Primary Tumor Cells by Camellia sinensis non fermentatum Extract Noviphenone (NPE®)

“…Fresh medium was added to each sample and either NPE ® (20, 30 ,40 and 100 μg/ml), Vitamin E 33 μM (VitE, D-α-Tocopherol polyethylene glycol 1000 succinate-TPGS; Sigma-Aldrich) and Vinblastine 22 nM (Merck KGaA, Darmstadt, Germany) were added and incubated for 1 h at 37˚C. Vinblastine and VitE TPGS were used as positive controls (51,52). Upon incubation with the desired substance, cells were collected and lysed in 120 μl of lysis buffer (0.75 M HCl, 0.2% Triton X in isopropanol) for 20 min at 37˚C shaking.…”

Design and Synthesis of Newly Synthesized Acrylamide Derivatives as Potential Chemotherapeutic Agents against MCF-7 Breast Cancer Cell Line Lodged on PEGylated Bilosomal Nano-Vesicles for Improving Cytotoxic Activity

“…Increasing the amount of DSPE-mPEG-2000 from 25 mg to 50mg predisposes it to a significant (p = 0.0169) decline in PS, where it is proclaimed previously that the elevation in PEG content permits a reasonable degree of steric hindrance resulting in the suppression of vesicular settling down and agglomeration, hence prohibiting vesicular aggregation and an increase in vesicular PS slows down the rate of vesicles' precipitation and, hence, hinders vesicles' agglomeration [37].…”

“…This might be related to the creation of highly porous membranes upon increasing the amount of DSPE-mPEG-2000 [35], resulting in lessened EE% values. In addition, the higher solubilization power of DSPE-mPEG-2000 upon increasing its amount will potentially increase the solubility of 4e, resulting in less encapsulation efficiency [37].…”

“…Thus, 4e-loaded PEGylated bilosome was assumed to serve as stabilized nano-vesicles for extended period of time and guided the rise in agglomeration of 4e at the tumor location [43]. These results may be accredited to the PEGylated layer that surrounds the vesicular surface, resulting in higher drug solubilization and increased rate of drug releases, and this due to the impact of hydrophilic and solubilization power of PEG to the drug [37]. Cytotoxic Activity of the Optimized Formula (F7) Compared to Target Compound 4e Cytotoxic activity against breast cancer MCF-7 cell line using MTT colorimetric assay was conducted for compound 4e in its pure form correlated to optimal 4e-loaded in the PEGylated bilosomal formula (F7), where the acquired IC 50 values were 2.11 µM for pure 4e and was significantly (p < 0.05) diminished at 0.75 ± 0.03 µM (Figure 16).…”

Design, Green Synthesis and Tailoring of Vitamin E TPGS Augmented Niosomal Nano-Carrier of Pyrazolopyrimidines as Potential Anti-Liver and Breast Cancer Agents with Accentuated Oral Bioavailability

“…Thus, both 2a and 7-loaded TPGS-modified niosomes are supposed to govern as stabilized nanovesicles for a prolonged period of time and aid in boosting clustering of the anti-cancer molecule 2a and 7 at the tumor site [47]. These outcomes may be owing to the TPGS layer that circumscribes the vesicular surface, predisposing it to a greater drug solubilization and release rate attributed to the influence of hydrophilic character and solubilization power of TPGS to the drug [39]. In order to investigate the superiority of TPGS-coated niosomes relative to the uncoated noisome and the pure unformulated molecules, the cytotoxic effect toward MCF-7 and HepG2 cell lines using the MTT colorimetric assay was performed.…”