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

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

Linhua Zhang,1 Dunwan Zhu,1 Xia Dong,1 Hongfan Sun,1 Cunxian Song,1 Chun Wang,2 Deling Kong1 1Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People’s Republic of China; 2Departmen...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Zhang L, Zhu D, Dong X, Sun H, Song C, Wang C, Kong D
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/d589a15c9c2348c58068999b41162369
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:d589a15c9c2348c58068999b41162369
record_format dspace
spelling oai:doaj.org-article:d589a15c9c2348c58068999b411623692021-12-02T05:10:44ZFolate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery1178-2013https://doaj.org/article/d589a15c9c2348c58068999b411623692015-03-01T00:00:00Zhttp://www.dovepress.com/folate-modified-lipidndashpolymer-hybrid-nanoparticles-for-targeted-pa-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Linhua Zhang,1 Dunwan Zhu,1 Xia Dong,1 Hongfan Sun,1 Cunxian Song,1 Chun Wang,2 Deling Kong1 1Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People’s Republic of China; 2Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA 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 Zhang LZhu DDong XSun HSong CWang CKong DDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2101-2114 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Zhang L
Zhu D
Dong X
Sun H
Song C
Wang C
Kong D
Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery
description Linhua Zhang,1 Dunwan Zhu,1 Xia Dong,1 Hongfan Sun,1 Cunxian Song,1 Chun Wang,2 Deling Kong1 1Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People’s Republic of China; 2Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA 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 
format article
author Zhang L
Zhu D
Dong X
Sun H
Song C
Wang C
Kong D
author_facet Zhang L
Zhu D
Dong X
Sun H
Song C
Wang C
Kong D
author_sort Zhang L
title Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery
title_short Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery
title_full Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery
title_fullStr Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery
title_full_unstemmed Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery
title_sort folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/d589a15c9c2348c58068999b41162369
work_keys_str_mv AT zhangl folatemodifiedlipidndashpolymerhybridnanoparticlesfortargetedpaclitaxeldelivery
AT zhud folatemodifiedlipidndashpolymerhybridnanoparticlesfortargetedpaclitaxeldelivery
AT dongx folatemodifiedlipidndashpolymerhybridnanoparticlesfortargetedpaclitaxeldelivery
AT sunh folatemodifiedlipidndashpolymerhybridnanoparticlesfortargetedpaclitaxeldelivery
AT songc folatemodifiedlipidndashpolymerhybridnanoparticlesfortargetedpaclitaxeldelivery
AT wangc folatemodifiedlipidndashpolymerhybridnanoparticlesfortargetedpaclitaxeldelivery
AT kongd folatemodifiedlipidndashpolymerhybridnanoparticlesfortargetedpaclitaxeldelivery
_version_ 1718400562957910016

Ejemplares similares