Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells

Dendritic cells (DCs) are promising targets for drug delivery, as they can induce immunity or tolerance. The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug a...

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Published in:International journal of nanomedicine 2016-01, Vol.11, p.3501-3516
Main Authors: Barbosa, João P, Neves, Ana R, Silva, Andreia M, Barbosa, Mário A, Reis, M Salette, Santos, Susana G
Format: Article
Language:English
Subjects:
Antigens
Antigens, CD - metabolism
Arthritis
Blood & organ donations
CD83 Antigen
Cell Differentiation - drug effects
Cytokines
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - metabolism
Drug Carriers - administration & dosage
Drug Carriers - chemistry
Drug Carriers - pharmacology
Drug delivery systems
Drugs
Flow Cytometry
Fluorescein
Fluorescein-5-isothiocyanate - chemistry
Humans
Immune Tolerance - drug effects
Immunoglobulins - metabolism
Interleukin-12 - metabolism
Lipids
Lipids - chemistry
Lipids - pharmacology
Membrane Glycoproteins - metabolism
Monocytes - metabolism
Nanoparticles
Nanostructures - administration & dosage
Nanostructures - chemistry
NF-kappa B - metabolism
Original Research
Resveratrol
Scanning electron microscopy
Stilbenes - administration & dosage
Stilbenes - pharmacology
Tumor necrosis factor
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-TNF
Vehicles
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container_title International journal of nanomedicine
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creator Barbosa, João P
Neves, Ana R
Silva, Andreia M
Barbosa, Mário A
Reis, M Salette
Santos, Susana G
description Dendritic cells (DCs) are promising targets for drug delivery, as they can induce immunity or tolerance. The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug activity. NLC were formulated incorporating the fluorochrome fluorescein isothiocyanate (FITC-NLC) or the natural anti-inflammatory molecule resveratrol (rsv-NLC). Primary human DCs were differentiated from peripheral blood monocytes, and the innovative imaging flow cytometry technique was used to examine FITC-NLC internalization. The capacity of rsv-NLC to inhibit DC activation in response to proinflammatory cytokine tumor necrosis factor-α (TNF- α) was investigated by conventional flow cytometry. A combination of imaging and conventional flow cytometry was used to assess NLC cytotoxicity. The results obtained indicate that both NLC formulations were stable over time, with mean diameter
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The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug activity. NLC were formulated incorporating the fluorochrome fluorescein isothiocyanate (FITC-NLC) or the natural anti-inflammatory molecule resveratrol (rsv-NLC). Primary human DCs were differentiated from peripheral blood monocytes, and the innovative imaging flow cytometry technique was used to examine FITC-NLC internalization. The capacity of rsv-NLC to inhibit DC activation in response to proinflammatory cytokine tumor necrosis factor-α (TNF- α) was investigated by conventional flow cytometry. A combination of imaging and conventional flow cytometry was used to assess NLC cytotoxicity. The results obtained indicate that both NLC formulations were stable over time, with mean diameter &lt;200 nm and highly negative zeta potential (about -30 mV). When DCs were placed in contact with NLC, imaging flow cytometry clearly showed that DCs efficiently internalized FITC-NLC, with nearly 100% of cells internalizing nanoparticles upon 1 hour of incubation. Both immature and mature DCs internalized NLC to high and comparable levels, and without cytotoxicity. Stimulating DC with TNF-α in the presence of rsv-NLC revealed that, using these nanoparticles, very small concentrations of rsv were sufficient to significantly decrease surface expression of activation marker CD83 (5 µM) and major histocompatibility complex-class II molecule human leukocyte antigen - antigen D related (10 µM), both upregulated in response to TNF-α stimulation. Rsv-NLC were compared with free rsv; at 5 µM, rsv-NLC were able to inhibit nuclear factor κ beta phosphorylation and significantly decrease the level of interleukin-12/23, both upregulated in response to TNF-α, while 10 µM free rsv were needed to promote a similar effect. 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subjects Antigens
Antigens, CD - metabolism
Arthritis
Blood & organ donations
CD83 Antigen
Cell Differentiation - drug effects
Cytokines
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - metabolism
Drug Carriers - administration & dosage
Drug Carriers - chemistry
Drug Carriers - pharmacology
Drug delivery systems
Drugs
Flow Cytometry
Fluorescein
Fluorescein-5-isothiocyanate - chemistry
Humans
Immune Tolerance - drug effects
Immunoglobulins - metabolism
Interleukin-12 - metabolism
Lipids
Lipids - chemistry
Lipids - pharmacology
Membrane Glycoproteins - metabolism
Monocytes - metabolism
Nanoparticles
Nanostructures - administration & dosage
Nanostructures - chemistry
NF-kappa B - metabolism
Original Research
Resveratrol
Scanning electron microscopy
Stilbenes - administration & dosage
Stilbenes - pharmacology
Tumor necrosis factor
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-TNF
Vehicles
title Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells
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