Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Li, Dan; Yang, Ke; Li, Jie-Si; Ke, Xiyu; Yu, De‐Quan; Du, Ran; Song, Ping; Yu, Kefu; Ren, Wei; Huang, Dan; Li, Xing-Huo; Hu, Xin; Zhang, Xuan; Zhang, Qiang

doi:10.2147/ijn.s38927

Cited by 10 publications

(8 citation statements)

References 38 publications

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“…We previous prepared a concentrated CLA-PTX microemulsion which containing dehydrated alcohol, Lipoid E 80, CrEL and soybean oil19. The concentration of CLA-PTX, CrEL, and Lipoid E80 in the concentrated microemulsion was 80, 95, and 190 mg/ml, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…CLA-PTX also exhibits a higher cellular uptake in C6 glioma and B16-F10 melanoma cells compared with paclitaxel. In addition, the anti-tumor activity of a CLA-PTX microemulsion and CLA-PTX-loaded iRGD modified liposomes was also confirmed in in vitro and in vivo experiments1921.…”

mentioning

confidence: 78%

“…The in vitro and in vivo anti-tumor activity of CLA-PTX has been confirmed in C6 glioma and B16-F10 melanoma cells181920. CLA-PTX also exhibits a higher cellular uptake in C6 glioma and B16-F10 melanoma cells compared with paclitaxel.…”

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confidence: 83%

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A self-assembling nanomedicine of conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) with higher drug loading and carrier-free characteristic

Zhong

Yao

Zhang

et al. 2016

Sci Rep

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The main objective of this study was to demonstrate the proof-of-principle for the hypothesis that conjugated linoleic acid-paclitaxel conjugate (CLA-PTX), a novel fatty acid modified anti-cancer drug conjugate, could self-assemble forming nanoparticles. The results indicated that a novel self-assembling nanomedicine, CLA-PTX@PEG NPs (about 105 nm), with Cremophor EL (CrEL)-free and organic solvent-free characteristics, was prepared by a simple precipitation method. Being the ratio of CLA-PTX:DSPE-PEG was only 1:0.1 (w/w), the higher drug loading CLA-PTX@PEG NPs (about 90%) possessed carrier-free characteristic. The stability results indicated that CLA-PTX@PEG NPs could be stored for at least 9 months. The safety of CLA-PTX@PEG NPs was demonstrated by the MTD results. The anti-tumor activity and cellular uptake were also confirmed in the in vitro experiments. The lower crystallinity, polarity and solubility of CLA-PTX compared with that of paclitaxel (PTX) might be the possible reason for CLA-PTX self-assembling forming nanoparticles, indicating a relationship between PTX modification and nanoparticles self-assembly. Overall, the data presented here confirm that this drug self-delivery strategy based on self-assembly of a CLA-PTX conjugate may offer a new way to prepare nanomedicine products for cancer therapy involving the relationship between anticancer drug modification and self-assembly into nanoparticles.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 78%

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A self-assembling nanomedicine of conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) with higher drug loading and carrier-free characteristic

Zhong

Yao

Zhang

et al. 2016

Sci Rep

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“…Our intracranial glioma model was established by directly injecting a mixture of glioma cells and matrigel into the caudatum. Compared with other commonly adopted models, where a cell suspension or tumor fragment [ 26 , 27 ] is injected directly into the caudatum, the use of matrigel prevents the cell suspension from refluxing and minimizes the development of extracranial tumors. Additionally, this unassisted or “hands-free” approach to intracranial tumor implantation not only improves tumor growth but also reduces procedure time and mortality.…”

Section: Discussionmentioning

confidence: 99%

Micheliolide Derivative DMAMCL Inhibits Glioma Cell Growth In Vitro and In Vivo

Guo

et al. 2015

PLoS ONE

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BackgroundThere is no highly effective chemotherapy for malignant gliomas to date. We found that dimethylaminomicheliolide (DMAMCL), a selective inhibitor of acute myeloid leukemia (AML) stem/progenitor cells, inhibited the growth of glioma cells.MethodsThe distribution of DMAMCL in brain was analyzed by an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS) system. The anti-tumor evaluations of DMAMCL in vitro were performed by MTT, FACS and RT-PCR. In vivo, the mixture of C6 cells and matrigel was injected into caudatum, and the anti-tumor activity of DMAMCL was evaluated by tumor growth and rat survival. The toxicity of DMAMCL was evaluated by body weight, daily food intake, hematological or serum biochemical analyses, and histological appearance of tissues.ResultsThe IC50 values of DMAMCL against the C6 and U-87MG cell lines in vitro were 27.18 ± 1.89 μM and 20.58 ± 1.61 μM, respectively. DAMMCL down-regulated the anti-apoptosis gene Bcl-2 and increased apoptosis in C6 and U-87MG cells in a dose-dependent manner. In a C6 rat tumor model, daily administration of DMAMCL for 21 days reduced the burden of C6 tumors by 60% to 88% compared to controls, and more than doubled the mean lifespan of tumor-bearing rats. Distribution analysis showed that the DMAMCL concentration was higher in the brain than in plasma. Evaluations for toxicity revealed that oral administration of DMAMCL at 200 or 300 mg/kg once a day for 21 days did not result in toxicity.ConclusionsThese results suggest that DMAMCL is highly promising for the treatment of glioma.

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“…More importantly, PALA exhibited a relatively low toxicity in vivo compared to PTX in terms of the body-weight change. The phenomenon can be attributed to the reason that the release of PTX from PALA is lower than Taxol ® since the process of decomposition of PALA was time-consuming, and the half-life of PALA is longer than PTX in vivo [32]. Moreover, the nutritional role of polyunsaturated fatty acids may resist the toxicity of PTX [33].…”

Section: Discussionmentioning

confidence: 99%

Synthetic low-density lipoprotein (sLDL) selectively delivers paclitaxel to tumor with low systemic toxicity

2016

Oncotarget

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Low density lipoprotein (LDL), which is a principal carrier for the delivery of cholesterol, has been used as a great candidate for the delivery of drugs to tumor based on the great requirements for cholesterol of many cancer cells. Mimicking the structure and composition of LDL, we designed a synthetic low-density lipoprotein (sLDL) to encapsulate paclitaxel-alpha linolenic acid (PALA) for tumor therapy. The PALA loaded sLDL (PALA-sLDL) and PALA-loaded microemulsion (PALA-ME, without the binding domain for LDLR) displayed uniform sizes with high drug loading efficiency (> 90%). In vitro studies demonstrated PALA-sLDL exhibited enhanced cellular uptake capacity and better cytotoxicity to LDLR over-expressed U87 MG cells as compared to PALA-ME. The uptake mechanisms of PALA-sLDL were involved in a receptor mediated endocytosis and macropinocytosis. Furthermore, the in vivo biodistribution and tumor growth inhibition studies of PALA-sLDL were investigated in xenograft U87 MG tumor-bearing mice. The results showed that PALA-sLDL exhibited higher tumor accumulation than PALA-ME and superior tumor inhibition efficiency (72.1%) compared to Taxol® (51.2%) and PALA-ME (58.8%) but with lower toxicity. These studies suggested that sLDL is potential to be used as a valuable carrier for the selective delivery of anticancer drugs to tumor with low systemic toxicity.

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Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Cited by 10 publications

References 38 publications

A self-assembling nanomedicine of conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) with higher drug loading and carrier-free characteristic

A self-assembling nanomedicine of conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) with higher drug loading and carrier-free characteristic

Micheliolide Derivative DMAMCL Inhibits Glioma Cell Growth In Vitro and In Vivo

Synthetic low-density lipoprotein (sLDL) selectively delivers paclitaxel to tumor with low systemic toxicity

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