Docetaxel-loaded PEO–PPO–PCL/TPGS mixed micelles for overcoming multidrug resistance and enhancing antitumor efficacy

Shi, Chunhuan; Zhang, Zhiqing; Wang, Fang; Ji, Xiaoqing; Zhao, Zhongxi; Luan, Yuxia

doi:10.1039/c5tb00401b

Cited by 41 publications

(13 citation statements)

References 43 publications

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“…Docetaxel (DTX) is one of the first-line anticancer drugs for solid tumours and is an antimitotic agent used in the cell cycle to promote tubulin polymerization and impede cells in the G2-M phase. [22,23] Nevertheless, its clinical application remains limited by low solubility, serious side effects, drug resistance and poor specificity. [24] The emergence of MDR has led to the failure of DTX in the treatment of cancer.…”

Section: Introductionmentioning

confidence: 99%

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

Fei

et al. 2019

Journal of Pharmacy and Pharmacology

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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.

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Section: Introductionmentioning

confidence: 99%

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

Fei

et al. 2019

Journal of Pharmacy and Pharmacology

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“…The mixed micelles showed negligible hemolytic potential (less than 5 %) to red blood cells (RBCs) even at the highest concentration of 2 mg mL −1 , which demonstrated that mixed micelles were blood‐compatible and safe for intravenous administration as well as their potential to be a drug delivery system. The excellent blood biocompatibility could be attributed to the outermost PEG shell, which serves as a protective layer …”

Section: Resultsmentioning

confidence: 90%

“…The excellentb loodb iocompatibility could be attributed to the outermost PEG shell,whichserves as aprotective layer. [28,29]…”

Section: Ex Vivo Hemolysis Assaysmentioning

confidence: 99%

Multifunctional Mixed Micelles for Efficient Docetaxol Delivery for Cancer Therapy

Zhang

et al. 2016

ChemPlusChem

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The objective of this study was to build mixed micelles based on two functional co‐polymers, including the redox‐sensitive polymer–drug conjugate methoxy poly(ethylene glycol)–poly(γ‐benzyl l‐glutamate)‐disulfide‐docetaxel (PEG–PBLG‐SS‐DTX) and the actively targeting methoxy poly(ethylene glycol)–folic acid (PEG–FA), for enhanced target specificity and improved anticancer efficiency of docetaxel (DTX). The spherical PEG–PBLG‐SS‐DTX/PEG–FA mixed micelles prepared by the dialysis method revealed a narrowly distributed size at 129.7±2.1 nm with low polydispersity of 0.10±0.02. Furthermore, the critical micelle concentration of the mixed micelles was 5.08 μg mL−1, indicating excellent self‐assembly ability in water and stability against dilution in blood circulation. The in vitro release study revealed that the conjugated DTX was rapidly released in response to dl‐dithiothreitol (DTT), a reducing agent. Only 12.3 % of DTX was released from the mixed micelles after 120 h in the absence of DTT. However, the accumulative release of DTX dramatically accelerated and reached more than 40 % in 120 h after addition of DTT. The in vitro cytotoxicity, cellular uptake and cell apoptosis experiments on the mixed micelles were performed using MTT assay, fluorescence inverted microscopy and flow cytometric analysis, and 4′,6‐diamidino‐2‐phenylindole (DAPI) staining, respectively, on folate receptor (FR)‐negative A549 and FR‐positive MCF‐7 cells. The mixed micelles could be taken up efficiently by MCF‐7 cells by FR‐mediated endocytosis compared with PEG–PBLG‐SS‐DTX micelles. Furthermore, remarkable cytotoxicity and cell apoptosis were identified for the mixed micelles against MCF‐7 cells, which was consistent with the results of the cellular uptake study. On the basis of these results, the redox‐sensitive PEG–PBLG‐SS‐DTX/PEG–FA mixed micelles using FA as a targeting ligand revealed prominent antitumor efficiency and might be a latent drug carrier for cancer chemotherapy.

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“…In the process of micellization, CMC was a key index to evaluate self-aggregation ability of micelles. The aggregation behavior of the material LC-SA/CS-SA in aqueous media was determined by fluorescence probe technique using pyrene as fluorescence probe (Shi et al, 2015). The curve of I 1 /I 3 value vs. the logarithmic concentration of the micelle material LC-SA/CS-SA is shown in Figure 5(A).…”

Section: Determination Of Cmcmentioning

confidence: 99%

l -Carnitine conjugated chitosan-stearic acid polymeric micelles for improving the oral bioavailability of paclitaxel

et al. 2020

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A delivery system based on L-carnitine (LC) conjugated chitosan (CS)-stearic acid polymeric micelles has been developed for improving the oral bioavailability of paclitaxel (PTX) through targeting intestinal organic cation/carnitine transporter 2 (OCTN2). Stearic acid grafted chitosan (CS-SA), as micelle skeleton material, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The PTX-loaded micelles were prepared by solvent evaporation-hydration method, and the ligand LC was conjugated onto the micelle surface by anchoring its derivative stearoyl group to the lipophilic core of micelle. The modified polymeric micelles showed regular spherical shapes with small particle size of 157.1 ± 5.2 nm and high drug loading capacity of 15.96 ± 0.20 wt%, and the micelle stability in water was supported by low critical micelle concentration of 14.31 ± 0.21 lg/ml. The drug-loaded micelles presented a slow and incomplete in vitro release, and the pharmacokinetic studies indicated the micelle carriers increased the relative bioavailability of PTX to 165.8% against the commercial formulation. The enhancement effect on intestinal absorption was also confirmed by the intracellular uptake of Caco-2 cells. The proposed micelle carrier system manifested a prospective tool for oral drug delivery.

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Docetaxel-loaded PEO–PPO–PCL/TPGS mixed micelles for overcoming multidrug resistance and enhancing antitumor efficacy

Abstract: A schematic diagram of DTX-loaded PEO–PPO–PCL/TPGS mixed micelles in vivo for overcoming multidrug resistance and enhancing antitumor efficacy.

Cited by 41 publications

References 43 publications

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

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

Multifunctional Mixed Micelles for Efficient Docetaxol Delivery for Cancer Therapy

l -Carnitine conjugated chitosan-stearic acid polymeric micelles for improving the oral bioavailability of paclitaxel

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