Stable loading and delivery of disulfiram with mPEG-PLGA/PCL mixed nanoparticles for tumor therapy

Song, Wantong; Tang, Zhaohui; Tian, Lei; Wen, Xue; Wang, Guanyi; Zhang, Dawei; Deng, Mingxiao; Tang, Xing; Chen, Xuesi

doi:10.1016/j.nano.2015.10.022

Cited by 74 publications

(44 citation statements)

References 53 publications

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“…Surface modified PLGA NPs with herceptin decreased the particle size depending on herceptin degradation (Yu et al, 2016). mPEG-PLGA/poly(ε-caprolactone) nanoparticles were slightly decreased the particle size in distilled after 96 h (Song et al, 2016).…”

Section: Characterization Of Cs-coated Plga-poloxamer Npsmentioning

confidence: 97%

Enhancing the in vitro anticancer activity of albendazole incorporated into chitosan-coated PLGA nanoparticles

Kang

Choi

Lee

et al. 2017

Carbohydrate Polymers

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Section: Characterization Of Cs-coated Plga-poloxamer Npsmentioning

confidence: 97%

Enhancing the in vitro anticancer activity of albendazole incorporated into chitosan-coated PLGA nanoparticles

Kang

Choi

Lee

et al. 2017

Carbohydrate Polymers

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“…43,44 Recently, it is reported that DSF could permanently inhibit P-gp activity by covalently modifying the cysteine residues in the nucleotide-binding domains of P-gp and/or block its maturation. 45,46 The influence of DSF on the intracellular accumulation of PTX and the P-gp-mediated drug efflux was investigated in both MCF-7 cells and MCF-7/ADR cells.…”

Section: Inhibition Of P-gp Analysismentioning

confidence: 99%

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

Huo¹,

Zhu²,

Niu³

et al. 2017

IJN

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Multidrug resistance (MDR) remains a major challenge for providing effective chemotherapy for many cancer patients. To address this issue, we report an intelligent polymer-based drug co-delivery system which could enhance and accelerate cellular uptake and reverse MDR. The nanodrug delivery systems were constructed by encapsulating disulfiram (DSF), a P-glyco-protein (P-gp) inhibitor, into the hydrophobic core of poly(ethylene glycol)- block -poly( l -lysine) (PEG- b -PLL) block copolymer micelles, as well as 2,3-dimethylmaleic anhydride (DMA) and paclitaxel (PTX) were grafted on the side chain of l -lysine simultaneously. The surface charge of the drug-loaded micelles represents as negative in plasma (pH 7.4), which is helpful to prolong the circulation time, and in a weak acid environment of tumor tissue (pH 6.5–6.8) it can be reversed to positive, which is in favor of their entering into the cancer cells. In addition, the carrier could release DSF and PTX successively inside cells. The results of in vitro studies show that, compared to the control group, the DSF and PTX co-loaded micelles with charge reversal exhibits more effective cellular uptake and significantly increased cytotoxicity of PTX to MCF-7/ADR cells which may be due to the inhibitory effect of DSF on the efflux function of P-gp. Accordingly, such a smart pH-sensitive nanosystem, in our opinion, possesses significant potential to achieve combinational drug delivery and overcome drug resistance in cancer therapy.

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“…To date, disulfiram was usually entrapped in the carrier system with relatively lower drug loading (,5.0%), and the highest value was achieved by Song et al (7.80%). 11 Thus, porous PLGA microparticle in the present research could realize the entrapment of disulfiram in a relatively ideal loading. Subsequently, the drug release profile of porous PLGA microparticles was studied, and a sustained release behavior of disulfiram could be clearly observed owing to the degradation of PLGA in PBS (Figure 2).…”

Section: Resultsmentioning

confidence: 84%

Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer

Wang¹,

Yang²,

Han³

et al. 2017

IJN

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In this study, poly(lactic- co -glycolic acid) (PLGA) was used as a carrier to construct disulfiram-loaded porous microparticle through the emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. The microparticle possessed highly porous surface, suitable aerodynamic diameter for inhalation (8.31±1.33 µm), favorable drug loading (4.09%±0.11%), and sustained release profile. The antiproliferation effect of release supernatant was detected through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using non-small-cell lung cancer A549 as a model, with only 13.3% of cell viability observed for the release supernatant at 7 days. The antiproliferation mechanism was elucidated to be associated with the enhanced induction of cell apoptosis and cell cycle arrest at S phase through flow cytometry and Western blotting analysis. Finally, wound healing and transwell migration assay showed that they could efficiently inhibit the cell migration. These results demonstrated that disulfiram-loaded porous PLGA microparticle could achieve favorable antitumor efficiency, implying the potential of treating non-small-cell lung cancer in a pulmonary administration.

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Stable loading and delivery of disulfiram with mPEG-PLGA/PCL mixed nanoparticles for tumor therapy

Cited by 74 publications

References 53 publications

Enhancing the in vitro anticancer activity of albendazole incorporated into chitosan-coated PLGA nanoparticles

Enhancing the in vitro anticancer activity of albendazole incorporated into chitosan-coated PLGA nanoparticles

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer

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