Self-Assembled Biodegradable Nanoparticles Developed by Direct Dialysis for the Delivery of Paclitaxel |
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Authors: | Jingwei?Xie Email author" target="_blank">Chi-Hwa?WangEmail author |
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Affiliation: | (1) Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117576, Singapore;(2) Molecular Engineering of Biological and Chemical Systems, Singapore-MIT Alliance, Singapore, 117576, Singapore |
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Abstract: | Purpose The main objective of this study was to obtain self-assembled biodegradable nanoparticles by a direct dialysis method for
the delivery of anticancer drug. The in vitro cellular particle uptake and cytotoxicity to C6 glioma cell line were investigated.
Methods Self-assembled anticancer drugs—paclitaxel-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) and poly(l-lactic acid) (PLA) nanoparticles—were achieved by direct dialysis. The physical and chemical properties of nanoparticles
were characterized by various state-of-the-art techniques. The encapsulation efficiency and in vitro release profile were measured by high-performance liquid chromatography. Particle cellular uptake was studied using confocal
microscopy, microplate reader, and flow cytometry. In addition, the cytotoxicity of this drug delivery system was evaluated
using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on C6 glioma cell line to predict the possible
dose response of paclitaxel-loaded PLGA and PLA nanoparticles.
Results PLGA and PLA nanoparticles with or without vitamin E tocopherol polyethylene glycol succinate (TPGS) as an additive were obtained,
in which the sustained release of paclitaxel of more than 20 days was achieved. The coumarin6-loaded PLGA and PLA nanoparticles
could penetrate the C6 glioma cell membrane and be internalized. The cytotoxicity of paclitaxel-loaded nanoparticles seemed
to be higher than that of commercial Taxol? after 3 days incubation when paclitaxel concentrations were 10 and 20 μg/ml.
Conclusions Direct dialysis could be employed to achieve paclitaxel-loaded PLGA and PLA nanoparticles, which could be internalized by
C6 glioma cells and enhance the cytotoxicity of paclitaxel because of its penetration to the cytoplasm and sustained release
property. |
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Keywords: | cellular uptake cytotoxicity dialysis nanoparticle paclitaxel |
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