Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone

Sang-Hyun Kim, Jun-Hyeok Moon, Seong-Un Jeong, Ho-Hyun Jung, Chan-Su Park, Bang Yeon Hwang, Chong-Kil LeeCollege of Pharmacy, Chungbuk National University, Cheongju, KoreaPurpose: Dexamethasone (Dex) has long been used as a potent immunosuppressive agent in the treatment of inflammatory and autoimmu...

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Autores principales: Kim SH, Moon JH, Jeong SU, Jung HH, Park CS, Hwang BY, Lee CK
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:eac98eab5b3141de91a23faab0982f462021-12-02T03:06:29ZInduction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone1178-2013https://doaj.org/article/eac98eab5b3141de91a23faab0982f462019-07-01T00:00:00Zhttps://www.dovepress.com/induction-of-antigen-specific-immune-tolerance-using-biodegradable-nan-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sang-Hyun Kim, Jun-Hyeok Moon, Seong-Un Jeong, Ho-Hyun Jung, Chan-Su Park, Bang Yeon Hwang, Chong-Kil LeeCollege of Pharmacy, Chungbuk National University, Cheongju, KoreaPurpose: Dexamethasone (Dex) has long been used as a potent immunosuppressive agent in the treatment of inflammatory and autoimmune diseases, despite serious side effects. In the present study, Dex and model antigen ovalbumin (OVA) were encapsulated with poly(lactic-co-glycolic acid) to deliver Dex and OVA preferentially to phagocytic cells, reducing systemic side effects of Dex. The OVA-specific immune tolerance-inducing activity of the nanoparticles (NPs) was examined.Methods: Polymeric NPs containing OVA and Dex (NP[OVA+Dex]) were prepared by the water-in-oil-in-water double emulsion solvent evaporation method. The effects of NP[OVA+Dex] on the maturation and function of immature dendritic cells (DCs) were examined in vitro. Furthermore, the OVA-specific immune tolerizing effects of NP[OVA+Dex] were confirmed in mice that were intravenously injected or orally fed with the NPs.Results: Immature DCs treated in vitro with NP[OVA+Dex] did not mature into immunogenic DCs but instead were converted into tolerogenic DCs. Furthermore, profoundly suppressed generation of OVA-specific cytotoxic T cells and production of OVA-specific IgG were observed in mice injected with NP[OVA+Dex], whereas regulatory T cells were concomitantly increased. Feeding of mice with NP[OVA+Dex] also induced OVA-specific immune tolerance.Conclusion: The present study demonstrates that oral feeding as well as intravenous injection of poly(lactic-co-glycolic acid) NPs encapsulating both antigen and Dex is a useful means of inducing antigen-specific immune tolerance, which is crucial for the treatment of autoimmune diseases.Keywords: polymeric nanoparticle, dexamethasone, ovalbumin, tolerogenic dendritic cell, antigen-specific immune toleranceKim SHMoon JHJeong SUJung HHPark CSHwang BYLee CKDove Medical PressarticlePolymeric nanoparticleDexamethasoneOvalbuminTolerogenic dendritic cellAntigen-specific immune toleranceMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5229-5242 (2019)
institution DOAJ
collection DOAJ
language EN
topic Polymeric nanoparticle
Dexamethasone
Ovalbumin
Tolerogenic dendritic cell
Antigen-specific immune tolerance
Medicine (General)
R5-920
spellingShingle Polymeric nanoparticle
Dexamethasone
Ovalbumin
Tolerogenic dendritic cell
Antigen-specific immune tolerance
Medicine (General)
R5-920
Kim SH
Moon JH
Jeong SU
Jung HH
Park CS
Hwang BY
Lee CK
Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone
description Sang-Hyun Kim, Jun-Hyeok Moon, Seong-Un Jeong, Ho-Hyun Jung, Chan-Su Park, Bang Yeon Hwang, Chong-Kil LeeCollege of Pharmacy, Chungbuk National University, Cheongju, KoreaPurpose: Dexamethasone (Dex) has long been used as a potent immunosuppressive agent in the treatment of inflammatory and autoimmune diseases, despite serious side effects. In the present study, Dex and model antigen ovalbumin (OVA) were encapsulated with poly(lactic-co-glycolic acid) to deliver Dex and OVA preferentially to phagocytic cells, reducing systemic side effects of Dex. The OVA-specific immune tolerance-inducing activity of the nanoparticles (NPs) was examined.Methods: Polymeric NPs containing OVA and Dex (NP[OVA+Dex]) were prepared by the water-in-oil-in-water double emulsion solvent evaporation method. The effects of NP[OVA+Dex] on the maturation and function of immature dendritic cells (DCs) were examined in vitro. Furthermore, the OVA-specific immune tolerizing effects of NP[OVA+Dex] were confirmed in mice that were intravenously injected or orally fed with the NPs.Results: Immature DCs treated in vitro with NP[OVA+Dex] did not mature into immunogenic DCs but instead were converted into tolerogenic DCs. Furthermore, profoundly suppressed generation of OVA-specific cytotoxic T cells and production of OVA-specific IgG were observed in mice injected with NP[OVA+Dex], whereas regulatory T cells were concomitantly increased. Feeding of mice with NP[OVA+Dex] also induced OVA-specific immune tolerance.Conclusion: The present study demonstrates that oral feeding as well as intravenous injection of poly(lactic-co-glycolic acid) NPs encapsulating both antigen and Dex is a useful means of inducing antigen-specific immune tolerance, which is crucial for the treatment of autoimmune diseases.Keywords: polymeric nanoparticle, dexamethasone, ovalbumin, tolerogenic dendritic cell, antigen-specific immune tolerance
format article
author Kim SH
Moon JH
Jeong SU
Jung HH
Park CS
Hwang BY
Lee CK
author_facet Kim SH
Moon JH
Jeong SU
Jung HH
Park CS
Hwang BY
Lee CK
author_sort Kim SH
title Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone
title_short Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone
title_full Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone
title_fullStr Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone
title_full_unstemmed Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone
title_sort induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/eac98eab5b3141de91a23faab0982f46
work_keys_str_mv AT kimsh inductionofantigenspecificimmunetoleranceusingbiodegradablenanoparticlescontainingantigenanddexamethasone
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AT jeongsu inductionofantigenspecificimmunetoleranceusingbiodegradablenanoparticlescontainingantigenanddexamethasone
AT junghh inductionofantigenspecificimmunetoleranceusingbiodegradablenanoparticlescontainingantigenanddexamethasone
AT parkcs inductionofantigenspecificimmunetoleranceusingbiodegradablenanoparticlescontainingantigenanddexamethasone
AT hwangby inductionofantigenspecificimmunetoleranceusingbiodegradablenanoparticlescontainingantigenanddexamethasone
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