PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery System

Macrophages possess an innate ability to scavenge heterogenous objects from the systemic circulation and to regulate inflammatory diseases in various organs via cytokine production. That makes them attractive targets for nanomedicine-based therapeutic approaches to inflammatory diseases. In the pres...

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Main Authors: Barbora Boltnarova, Jana Kubackova, Josef Skoda, Alzbeta Stefela, Monika Smekalova, Petra Svacinova, Ivona Pavkova, Milan Dittrich, Daniel Scherman, Jarmila Zbytovska, Petr Pavek, Ondrej Holas
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/11/3/749
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author Barbora Boltnarova
Jana Kubackova
Josef Skoda
Alzbeta Stefela
Monika Smekalova
Petra Svacinova
Ivona Pavkova
Milan Dittrich
Daniel Scherman
Jarmila Zbytovska
Petr Pavek
Ondrej Holas
author_facet Barbora Boltnarova
Jana Kubackova
Josef Skoda
Alzbeta Stefela
Monika Smekalova
Petra Svacinova
Ivona Pavkova
Milan Dittrich
Daniel Scherman
Jarmila Zbytovska
Petr Pavek
Ondrej Holas
author_sort Barbora Boltnarova
collection DOAJ
description Macrophages possess an innate ability to scavenge heterogenous objects from the systemic circulation and to regulate inflammatory diseases in various organs via cytokine production. That makes them attractive targets for nanomedicine-based therapeutic approaches to inflammatory diseases. In the present study, we have prepared several different poly(lactic-co-glycolic acid) (PLGA) polymer nanospheres for macrophage-targeted drug delivery using both nanoprecipitation and emulsification solvent evaporation methods. Two experimental linear PLGA polymers with relatively low molar weight, one experimental branched PLGA with unique star-like molecular architecture, and a commercially available PLGA, were used for nanosphere formulation and compared to their macrophage uptake capacity. The nanosphere formulations labelled with loaded fluorescent dye Rhodamine B were further tested in mouse bone marrow-derived macrophages and in hepatocyte cell lines AML-12, HepG2. We found that nanospheres larger than 100 nm prepared using nanoprecipitation significantly enhanced distribution of fluorescent dye selectively into macrophages. No effects of nanospheres on cellular viability were observed. Additionally, no significant proinflammatory effect after macrophage exposure to nanospheres was detected as assessed by a determination of proinflammatory cytokines <i>Il-1β</i> and <i>Tnfα</i> mRNA. All experimental PLGA nanoformulations surpassed the nanospheres obtained with the commercially available polymer taken as a control in their capacity as macrophage-specific carriers.
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spelling doaj.art-035f8cab806046ac9246a965110ad88a2023-11-21T10:45:52ZengMDPI AGNanomaterials2079-49912021-03-0111374910.3390/nano11030749PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery SystemBarbora Boltnarova0Jana Kubackova1Josef Skoda2Alzbeta Stefela3Monika Smekalova4Petra Svacinova5Ivona Pavkova6Milan Dittrich7Daniel Scherman8Jarmila Zbytovska9Petr Pavek10Ondrej Holas11Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Molecular Pathology and Biology, Faculty of Military Health Science, University of Defence in Brno, Trebesska 1575, 500 01 Hradec Kralove, Czech RepublicDepartment of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicCentre National de la Recherche Scientifique (CNRS), 3 rue Michel-Ange, 75016 Paris, FranceDepartment of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicMacrophages possess an innate ability to scavenge heterogenous objects from the systemic circulation and to regulate inflammatory diseases in various organs via cytokine production. That makes them attractive targets for nanomedicine-based therapeutic approaches to inflammatory diseases. In the present study, we have prepared several different poly(lactic-co-glycolic acid) (PLGA) polymer nanospheres for macrophage-targeted drug delivery using both nanoprecipitation and emulsification solvent evaporation methods. Two experimental linear PLGA polymers with relatively low molar weight, one experimental branched PLGA with unique star-like molecular architecture, and a commercially available PLGA, were used for nanosphere formulation and compared to their macrophage uptake capacity. The nanosphere formulations labelled with loaded fluorescent dye Rhodamine B were further tested in mouse bone marrow-derived macrophages and in hepatocyte cell lines AML-12, HepG2. We found that nanospheres larger than 100 nm prepared using nanoprecipitation significantly enhanced distribution of fluorescent dye selectively into macrophages. No effects of nanospheres on cellular viability were observed. Additionally, no significant proinflammatory effect after macrophage exposure to nanospheres was detected as assessed by a determination of proinflammatory cytokines <i>Il-1β</i> and <i>Tnfα</i> mRNA. All experimental PLGA nanoformulations surpassed the nanospheres obtained with the commercially available polymer taken as a control in their capacity as macrophage-specific carriers.https://www.mdpi.com/2079-4991/11/3/749PLGAnanospheresnanoparticlesnanoprecipitationinflammationmacrophages
spellingShingle Barbora Boltnarova
Jana Kubackova
Josef Skoda
Alzbeta Stefela
Monika Smekalova
Petra Svacinova
Ivona Pavkova
Milan Dittrich
Daniel Scherman
Jarmila Zbytovska
Petr Pavek
Ondrej Holas
PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery System
Nanomaterials
PLGA
nanospheres
nanoparticles
nanoprecipitation
inflammation
macrophages
title PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery System
title_full PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery System
title_fullStr PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery System
title_full_unstemmed PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery System
title_short PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery System
title_sort plga based nanospheres as a potent macrophage specific drug delivery system
topic PLGA
nanospheres
nanoparticles
nanoprecipitation
inflammation
macrophages
url https://www.mdpi.com/2079-4991/11/3/749
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