A Novel Docetaxel-Loaded Poly (ε-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

Mei, Lin; Zhang, Yangqing; Zheng, Yi; Tian, Ge; Song, Cunxian; Yang, Dongxu; Chen, Hongli; Sun, Hongfan; Tian, Ye; Liu, Kexin; Li, Zhen; Huang, Laiqiang

doi:10.1007/s11671-009-9431-6

Cited by 118 publications

(84 citation statements)

References 37 publications

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“…[14][15][16][17] However, in recent studies by Zhang et al, 16 blank Pluronic P123/F127 mixed polymeric micelles were demonstrated to be toxic at relatively low concentrations (0.1% w/v) compared to the copolymers investigated in this study, which do not induce cytotoxicity below 1% w/v. We suggest that the greater cellular biocompatibility along with the biodegradability of MePEG-b-PCL may be a potential advantage, allowing for higher dosing of drug and copolymer.…”

Section: Cytotoxicity Of Ptx-loaded Nanoparticlescontrasting

confidence: 56%

“…13 This led to several reports evaluating multicomponent or mixed polymeric nanoparticles incorporating one or more Pluronics for both solubilizing taxanes and inhibiting P-gp function. [14][15][16][17] However, the potential drawback of using Pluronics is the nondegradability and lack of renal excretion for high-molecular-weight members of this copolymer class. 18,19 Previous work by our group has demonstrated that a very low-molecular-weight MePEG-b-PCL copolymer (MePEG 17 -b-PCL 5 [PCL5]) is an effective modulator of P-gp.…”

Section: Introductionmentioning

confidence: 99%

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The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Wan¹,

Letchford²,

Jackson³

et al. 2013

IJN

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Two types of nanoparticles were prepared using the diblock copolymer methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL), with either a short PCL block length, which forms micelles, or with a longer PCL block length, which forms kinetically "frozen core" structures termed nanospheres. Paclitaxel (PTX)-loaded micelles and nanospheres were evaluated for their cytotoxicity, cellular polymer uptake, and drug accumulation in drug-sensitive (Madin-Darby Canine Kidney [MDCK]II) and multidrug-resistant (MDR) P-glycoprotein (P-gp)-overexpressing (MDCKII-MDR1) cell lines. Both types of PTX-loaded nanoparticles were equally effective at inhibiting proliferation of MDCKII cells, but PTX-loaded micelles were more cytotoxic than nanospheres in MDCKII-MDR1 cells. The intracellular accumulation of both PTX and the diblock copolymers were similar for both nanoparticles, suggesting that the difference in cytotoxicity might be due to the different drug-release profiles. Furthermore, the cytotoxicity of these PTX-loaded nanoparticles was enhanced when these systems were subsequently or concurrently combined with a low-molecular-weight MePEG-b-PCL diblock copolymer, which we have previously demonstrated to be an effective P-gp inhibitor. These results suggest that the dual functionality of MePEG-b-PCL might be useful in delivering drug intracellularly and in modulating P-gp in order to optimize the cytotoxicity of PTX in multidrug-resistant cells.

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Section: Cytotoxicity Of Ptx-loaded Nanoparticlescontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Wan¹,

Letchford²,

Jackson³

et al. 2013

IJN

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“…In contrast, the obviously enhanced cytotoxicity of MTX via the nano-sized particles means that there was a significant reverse effect of drug resistance. NPs could reduce the MDR that characterizes many anticancer drugs by a mechanism of cell internalization of the drug by endocytosis [42], by lowering drug efflux from the cells [43] and/or by allowing pH-dependent drug release from the endosomes to cell cytosol [44]. As demonstrated in Section 3.5, the pH-sensitivity of NPs allowed their rapid escape from the endosomal compartment, which may enhance their therapeutic efficiency compared to the native drug.…”

Section: Discussionmentioning

confidence: 99%

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

et al. 2013

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Nanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from N α ,N ε -dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX-CS-NPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX-CS-NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy.

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“…31,32 In addition, from the zeta potential measurement, we can estimate the dominant component on the particles' surface. 33 The zeta potential of the drug loaded PCEP NPs, LPNPs, and FLPNPs (Table 1) indicates the negative charges on the nanoparticle surface. LPNPs and FLPNPs showed higher negative zeta potential value than that of PCEP NPs.…”

Section: Characterization Of the Nanoparticlesmentioning

confidence: 99%

Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery

Zhang

Zhu

Dong

et al. 2015

IJN

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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.

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A Novel Docetaxel-Loaded Poly (ε-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

Cited by 118 publications

References 37 publications

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery

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A Novel Docetaxel-Loaded Poly (ε-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

Cited by 118 publications

References 37 publications

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

Folate-modified lipid&ndash;polymer hybrid nanoparticles for targeted paclitaxel delivery

Contact Info

Product

Resources

About

Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery