Induction of antigen-specific immune tolerance using biodegradable nanoparticles containing antigen and dexamethasone
Received 2 April 2019
Accepted for publication 4 June 2019
Published 12 July 2019 Volume 2019:14 Pages 5229—5242
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo
Sang-Hyun Kim, Jun-Hyeok Moon, Seong-Un Jeong, Ho-Hyun Jung, Chan-Su Park, Bang Yeon Hwang, Chong-Kil Lee
College of Pharmacy, Chungbuk National University, Cheongju, Korea
Purpose: 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
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