Enhanced antitumor efficacy by Paclitaxel-loaded Pluronic P123/F127 mixed micelles against non-small cell lung cancer based on passive tumor targeting and modulation of drug resistance

Zhang, Wei; Shi, Yuan; Chen, Yanzuo; Yu, Shuangyin; Hao, Junguo; Luo, Jieqi; Sha, Xianyi; Fang, Xiaoling

doi:10.1016/j.ejpb.2010.04.017

Cited by 171 publications

(83 citation statements)

References 65 publications

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“…The KBv xenograft mice model was established by inoculating 5×10 6 KBv cells (in 0.2 mL of pH 7.4 PBS) subcutaneously into the right hind leg. When tumor size reached 1 cm 3 in diameter, tumor-bearing mice were injected with 100 μL of DIR-labeled mixed micelles (DIR content: 0.2%) via the tail vein.…”

Section: Tissue Distribution Studiesmentioning

confidence: 99%

“…The antitumor efficacy of different MTX formulations was evaluated in KBv tumor-bearing mice model, which was established by inoculating 0.2 mL of PBS containing 5×10 6 KBv cells subcutaneously in the right hind leg of the mice. The first dose was scheduled at 24 hours after tumor inoculation 3,4 (designated as day 0).…”

Section: In Vivo Antitumor Efficacy and Safety Evaluationmentioning

confidence: 99%

“…Compared to single Pluronic P105 micelles, the micelles comprising Pluronic P105 and F127 can be more stable, due to the lowered critical micelle concentration conferred by the high PEO-poly(propylene oxide) ratio of F127, which will contribute to the long retention of drug-loaded micelles in blood, and eventually achieve higher drug accumulation at the target site (tumor) through the EPR effect. [6][7][8] It is noteworthy that doxorubicin-loaded mixed micelles composed of Pluronic L61 and F127 (SP1049C) have already reached Phase III stage. 9 However, a major obstacle to the conventional drug delivery systems has been found to be the nonspecific uptake by reticuloendothelial system (RES).…”

Section: Introductionmentioning

confidence: 99%

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The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment

Chen¹,

Zhang²,

Huang³

et al. 2015

IJN

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The therapeutic effect of methotrexate (MTX)-conjugated Pluronic-based polymeric mixed micelles (F127/P105-MTX) on the folate receptor-overexpressing tumors treatment was investigated in this study. Due to its high structural similarity to folic acid and the high expression of folate receptor in most solid tumors, MTX serves as not only a cytotoxic agent but also a homing ligand. Cellular uptake and the endocytic mechanism studies of MTX-conjugated mixed micelles were performed in folate receptor-rich KBv and folate receptor-deficient A-549 cancer cells. Additionally, the efficacy and safety studies of F127/P105-MTX in KBv tumor-bearing mice were evaluated. Results indicate that F127/P105-MTX significantly enhanced the cellular uptake in KBv cells as compared to that of conventional non-MTX-conjugated mixed micelles. Moreover, the results showed that F127/P105-MTX can be internalized by both caveolae- and clathrin-mediated endocytosis in energy-dependent and folate receptor-dependent manners. The in vitro and in vivo antitumor efficacies of F127/P105-MTX were significantly enhanced in comparison with MTX-entrapped mixed micelles. Furthermore, no acute toxicities to hematological system and major organs have been observed after intravenous administration during the regimen. Therefore, our results suggest that F127/P105-MTX could be an effective and safe nano-drug delivery system for cancer therapy, especially for the folate receptor-rich cancer treatment.

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Section: Tissue Distribution Studiesmentioning

confidence: 99%

Section: In Vivo Antitumor Efficacy and Safety Evaluationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment

Chen¹,

Zhang²,

Huang³

et al. 2015

IJN

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“…32,33 For micellelabeling experiments, 0.05% of rhodamine-labeled P407 to unlabeled P407/aCSF was determined to be optimal for fluorescent-imaging purposes.…”

Section: Synthesis Of Rhodamine-labeled P407 Nano-micellesmentioning

confidence: 99%

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

Singleton¹,

Collins²,

Bienemann³

et al. 2017

IJN

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Background The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood–brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). Materials and methods The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. Results Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P <0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. Conclusion CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic.

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“…29,30 Notable examples include the use of folic acid functionalised P123/F127 mixed nanocarriers for paclitaxel delivery in multidrug resistant tumours and thermally responsive F127-chitosan nanocarriers for the intracellular delivery of small molecules. [31][32][33] Significantly, cationic F127-PEI conjugates have been shown to improve both the delivery of the anti-cancer compound docetaxel and a plasmid encoding the serine protease inhibitor TFPI-2. 34 These examples highlight the adaptability of Pluronic nanocarrier systems functionalised with small molecules, proteins or polymers as drug or gene delivery vectors.…”

Section: -15mentioning

confidence: 99%

Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia

et al. 2017

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Accordingly, we describe the synthesis, characterisation and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide.The drug-loaded particles are produced via an emulsion-to-micelle transition method and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukaemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukaemia.3

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Enhanced antitumor efficacy by Paclitaxel-loaded Pluronic P123/F127 mixed micelles against non-small cell lung cancer based on passive tumor targeting and modulation of drug resistance

Cited by 171 publications

References 65 publications

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia

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Enhanced antitumor efficacy by Paclitaxel-loaded Pluronic P123/F127 mixed micelles against non-small cell lung cancer based on passive tumor targeting and modulation of drug resistance

Cited by 171 publications

References 65 publications

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on&nbsp;the folate receptor-rich tumors treatment

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on&nbsp;the folate receptor-rich tumors treatment

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia

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Product

Resources

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The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment