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Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice

To improve the oral efficiency of exenatide, we prepared polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for exenatide oral delivery. Exenatide was encapsulated into the NPs by the w/o/w emulsion-solvent evaporation method. The particle size of the NPs-Fc w...

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Autores principales: Shi, Yanan, Sun, Xinfeng, Zhang, Liping, Sun, Kaoxiang, Li, Keke, Li, Youxin, Zhang, Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768888/
https://www.ncbi.nlm.nih.gov/pubmed/29335533
http://dx.doi.org/10.1038/s41598-018-19170-y
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author Shi, Yanan
Sun, Xinfeng
Zhang, Liping
Sun, Kaoxiang
Li, Keke
Li, Youxin
Zhang, Qiang
author_facet Shi, Yanan
Sun, Xinfeng
Zhang, Liping
Sun, Kaoxiang
Li, Keke
Li, Youxin
Zhang, Qiang
author_sort Shi, Yanan
collection PubMed
description To improve the oral efficiency of exenatide, we prepared polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for exenatide oral delivery. Exenatide was encapsulated into the NPs by the w/o/w emulsion-solvent evaporation method. The particle size of the NPs-Fc was approximately 30 nm larger than that of the unmodified NPs with polydispersity indices in a narrow range (PDIs; PDI < 0.3) as detected by DLS, and the highest encapsulation efficiency of exenatide in the NPs was greater than 80%. Fc-conjugated NPs permeated Caco-2 cells faster and to a greater extent compared to unmodified NPs, as verified by CLSM and flow cytometry. Hypoglycemic effect studies demonstrated that oral administration of exenatide-loaded PEG-PLGA NPs modified by an Fc group extended the hypoglycemic effects compared with s.c. injection of the exenatide solution. Fluorescence-labeled NPs were used to investigate the effects of Fc targeting, and the results demonstrated that the NPs-Fc stayed in the gastrointestinal tract for a longer time in comparison with the unmodified NPs, as shown by the whole-body fluorescence images and fluorescence images of the dissected organs detected by in vivo imaging in live mice. Therefore, Fc-targeted nano-delivery systems show great promise for oral peptide/protein drug delivery.
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spelling pubmed-57688882018-01-25 Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice Shi, Yanan Sun, Xinfeng Zhang, Liping Sun, Kaoxiang Li, Keke Li, Youxin Zhang, Qiang Sci Rep Article To improve the oral efficiency of exenatide, we prepared polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for exenatide oral delivery. Exenatide was encapsulated into the NPs by the w/o/w emulsion-solvent evaporation method. The particle size of the NPs-Fc was approximately 30 nm larger than that of the unmodified NPs with polydispersity indices in a narrow range (PDIs; PDI < 0.3) as detected by DLS, and the highest encapsulation efficiency of exenatide in the NPs was greater than 80%. Fc-conjugated NPs permeated Caco-2 cells faster and to a greater extent compared to unmodified NPs, as verified by CLSM and flow cytometry. Hypoglycemic effect studies demonstrated that oral administration of exenatide-loaded PEG-PLGA NPs modified by an Fc group extended the hypoglycemic effects compared with s.c. injection of the exenatide solution. Fluorescence-labeled NPs were used to investigate the effects of Fc targeting, and the results demonstrated that the NPs-Fc stayed in the gastrointestinal tract for a longer time in comparison with the unmodified NPs, as shown by the whole-body fluorescence images and fluorescence images of the dissected organs detected by in vivo imaging in live mice. Therefore, Fc-targeted nano-delivery systems show great promise for oral peptide/protein drug delivery. Nature Publishing Group UK 2018-01-15 /pmc/articles/PMC5768888/ /pubmed/29335533 http://dx.doi.org/10.1038/s41598-018-19170-y Text en © The Author(s) 2018 https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Shi, Yanan
Sun, Xinfeng
Zhang, Liping
Sun, Kaoxiang
Li, Keke
Li, Youxin
Zhang, Qiang
Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice
title Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice
title_full Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice
title_fullStr Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice
title_full_unstemmed Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice
title_short Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice
title_sort fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768888/
https://www.ncbi.nlm.nih.gov/pubmed/29335533
http://dx.doi.org/10.1038/s41598-018-19170-y
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