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Title: Folic acid-modified methotrexate-conjugated PEGylated poly(ε- caprolactone) nanoparticles for targeted delivery
Authors: Ousanee Issarachot
Jiraphong Suksiriworapong
Mikihisa Takano
Ryoko Yumoto
Varaporn Buraphacheep Junyaprasert
Mahidol University
Hiroshima University
Keywords: Chemical Engineering;Chemistry;Materials Science;Mathematics;Physics and Astronomy
Issue Date: 1-Feb-2014
Citation: Journal of Nanoparticle Research. Vol.16, No.2 (2014)
Abstract: Functionalized nanoparticles of polymer-drug conjugates of PEGylated poly(ε-caprolactone) (PEGylated P(CL)) with methotrexate (MTX) and folic acid (FOL) were developed and investigated for their targeting efficiency. FOL- and MTX-conjugated PEGylated P(CL) copolymers were employed to prepare P(MTXCLCL)2-PEG NPs and FOL-P(MTXCLCL)2-PEG NPs. By varying the amount of MTX, the different characteristics of nanoparticles were obtained. The results showed that an increase in particle size and more negative surface charge of P(MTXCLCL)2-PEG NPs were related to an increased amount of MTX along the polymer backbone. After being decorated with FOL, the particle size increased by nearly twofolds while the zeta potential decreased. All nanoparticles were spherical as observed under SEM micrographs. The release profiles showed pH-dependent and sustained release over 20 days. Higher extent of MTX was released in pH 4.5 medium as compared to the drug release in pH 7.4 medium. All nanoparticles showed greater toxicity to MCF-7 cells than A549 cells. In addition, FOL-P(MTXCLCL)2-PEG NPs exhibited the highest toxicity to MCF-7 cells as compared to all P(MTXCLCL)2-PEG NPs and free MTX. Furthermore, FOL-P(MTXCLCL)2-PEG NPs were internalized into MCF-7 cells higher than P(MTXCLCL)2-PEG NPs and FOL-P(MTXCLCL)2-PEG NPs incubated with free FOL. The results indicated that FOL-P(MTXCLCL)2-PEG NPs efficiently entered into MCF-7 cells via folate receptor-mediated endocytosis together with adsorptive endocytosis. Graphical Abstract: [Figure not available: see fulltext.] © 2014 Springer Science+Business Media Dordrecht.
ISSN: 1572896X
Appears in Collections:Scopus 2011-2015

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