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Nanoparticles of 2-deoxy-d-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment

Paper ID Volume ID Publish Year Pages File Format Full-Text
6242 468 2014 12 PDF Available
Title
Nanoparticles of 2-deoxy-d-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment
Abstract

Based on the facilitative glucose transporter (GLUT) over-expression on both blood–brain barrier (BBB) and glioma cells, 2-deoxy-d-glucose modified poly(ethylene glycol)-co-poly(trimethylene carbonate) nanoparticles (dGlu–NP) were developed as a potential dual-targeted drug delivery system for enhancing the BBB penetration via GLUT-mediated transcytosis and improving the drug accumulation in the glioma via GLUT-mediated endocytosis. In vitro physicochemical characterization of the dual-targeted nanoparticulate system presented satisfactory size of 71 nm with uniform distribution, high encapsulation efficiency and adequate loading capacity of paclitaxel (PTX). Compared with non-glucosylated nanoparticles (NP), a significantly higher amount of dGlu–NP was internalized by RG-2 glioma cells through caveolae-mediated and clathrin-mediated endocytosis. Both of the transport ratios across the in vitro BBB model and the cytotoxicity of RG-2 cells after crossing the BBB were significantly greater of dGlu–NP/PTX than that of NP/PTX. In vivo fluorescent image indicated that dGlu–NP had high specificity and efficiency in intracranial tumor accumulation. The anti-glioblastoma efficacy of dGlu–NP/PTX was significantly enhanced in comparison with that of Taxol and NP/PTX. Preliminary safety tests showed no acute toxicity to hematological system, liver, kidney, heart, lung and spleen in mice after intravenous administration at a dose of 100 mg/kg blank dGlu–NP per day for a week. Therefore, these results indicated that dGlu–NP developed in this study could be a potential dual-targeted vehicle for brain glioma therapy.

Keywords
Glioma; Dual-targeted drug delivery system; Glucose transporter; Endocytic mechanism; Avascular glioma spheroids
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Nanoparticles of 2-deoxy-d-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 1, January 2014, Pages 518–529
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us