title: [Transport of PLGA nanoparticles across Caco-2/HT29-MTX co-cultured cells].
abstract: The present study is to establish Caco-2/HT29-MTX co-cultured cells and investigate the transport capability of PLGA nanoparticles with different surface chemical properties across Caco-2/HT29-MTX co-cultured cells. PLGA-NPs, mPEG-PLGA-NPs and chitosan coated PLGA-NPs were prepared by nanoprecipitation method using poly(lactic-co-glycolic acid) as carrier material with surface modified by methoxy poly(ethylene glycol) and chitosan. The particle size and zeta potential of nanoparticles were measured by dynamic light scattering. Coumarin 6 was used as a fluorescent marker in the transport of nanoparticles investigated by confocal laser scanning microscopy. The transport of furanodiene (FDE) loaded nanoparticles was quantitively determined by high performance liquid chromatography. Colchicine and nocodazole were used in the transport study to explore the involved endocytosis mechanisms of nanoparticles. Distribution of the tight junction proteins ZO-1 was also analyzed by immunofluorescence staining. The results showed that the nanoparticles dispersed uniformly. The zeta potential of PLGA-NPs was negative, the mPEG-PLGA-NPs was close to neutral and the CS-PLGA-NPs was positive. The entrapment efficiency of FDE in all nanoparticles was higher than 75%. The transport capability of mPEG-PLGA-NPs across Caco-2/HT29-MTX co-cultured cells was higher than that of PLGA-NPs and CS-PLGA-NPs. Colchicine and nocodazole could significantly decrease the transport amount of nanoparticles. mPEG-PLGA-NPs could obviously reduce the distribution of ZO-1 protein than PLGA-NPs and CS-PLGA-NPs. The transport mechanism of PLGA-NPs and mPEG-PLGA-NPs were indicated to be a combination of endocytosis and paracellular way, while CS-PLGA-NPs mainly relied on the endocytosis way. PEG coating could shield the surface charge and enhance the hydrophilicity of PLGA nanoparticles, which leads mPEG-PLGA-NPs to possess higher anti-adhesion activity. As a result, mPEG-PLGA-NPs could penetrate the mucus layer rapidly and transport across Caco-2/HT29-MTX co-cultured cells.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wen
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Dong-Hai
authors.initials: DH
authors.lastname: Lin
authors.forename: Jun-Teng
authors.initials: JT
authors.lastname: Wang
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Qin
authors.forename: Gui-Ping
authors.initials: GP
authors.lastname: Guo
mesh_terms: D001692:Biological Transport; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D018920:Coculture Techniques; D004337:Drug Carriers; D005663:Furans / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D019073:HT29 Cells; D006574:Heterocyclic Compounds, 2-Ring / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; D062826:Zonula Occludens-1 Protein; C442489:furanodiene; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D048271:Chitosan