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已发表论文
叶酸修饰脂质聚合物复合纳米粒子用于紫杉醇的靶向递送
Authors Zhang L, Zhu D, Dong X, Sun H, Song C, Wang C, Kong D
Published Date March 2015 Volume 2015:10 Pages 2101—2114
DOI http://dx.doi.org/10.2147/IJN.S77667
Received 17 November 2014, Accepted 22 January 2015, Published 16 March 2015
Abstract: The purpose of this study was to develop a novel lipid–polymer hybrid
drug carrier comprised of folate (FA) modified lipid-shell and polymer-core
nanoparticles (FLPNPs) for sustained, controlled, and targeted delivery of
paclitaxel (PTX). The core-shell NPs consist of 1) a poly(ε-caprolactone)
hydrophobic core based on self-assembly of poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone)
(PCL-PEG-PCL) amphiphilic copolymers, 2) a lipid monolayer formed with
1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N -[methoxy
(polyethylene glycol)-2000] (DSPE-PEG2000), 3) a targeting ligand (FA) on the
surface, and were prepared using a thin-film hydration and ultrasonic
dispersion method. Transmission electron microscopy and dynamic light
scattering analysis confirmed the coating of the lipid monolayer on the
hydrophobic polymer core. Physicochemical characterizations of PTX-loaded
FLPNPs, such as particle size and size distribution, zeta potential,
morphology, drug loading content, encapsulation efficiency, and in vitro drug
release, were also evaluated. Fluorescent microscopy proved the internalization
efficiency and targeting ability of the folate conjugated on the lipid
monolayer for the EMT6 cancer cells which overexpress folate receptor. In vitro
cytotoxicity assay demonstrated that the cytotoxic effect of PTX-loaded FLPNPs
was lower than that of Taxol®, but higher than that of PTX-loaded LPNPs
(without folate conjugation). In EMT6 breast tumor model, intratumoral
administration of PTX-loaded FLPNPs showed similar antitumor efficacy but low
toxicity compared to Taxol®. More importantly, PTX-loaded FLPNPs
showed greater tumor growth inhibition (65.78%) than the nontargeted PTX-loaded
LPNPs (48.38%) (P <0.05). These findings
indicated that the PTX loaded-FLPNPs with mixed lipid monolayer shell and
biodegradable polymer core would be a promising nanosized drug formulation for
tumor-targeted therapy.
Keywords: lipid–polymer hybrid nanoparticles, paclitaxel, drug delivery, PCL-PEG-PCL, folate
Keywords: lipid–polymer hybrid nanoparticles, paclitaxel, drug delivery, PCL-PEG-PCL, folate
