A silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-1

Wei Qu,1,2 Yong Li,2,* Lars Hovgaard,3 Song Li,1 Wenbin Dai,1 Jiancheng Wang,1 Xuan Zhang,1 Qiang Zhang1,*1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, PR China; 2Department of Nutrition and Food Hygiene, Peking University Healt...

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Autores principales:	Qu W, Li Y, Hovgaard L, Li S, Dai W, Wang J, Zhang X, Zhang Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fbaae50d237841e6b552403156edff07
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spelling	oai:doaj.org-article:fbaae50d237841e6b552403156edff072021-12-02T01:33:11ZA silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-11176-91141178-2013https://doaj.org/article/fbaae50d237841e6b552403156edff072012-09-01T00:00:00Zhttp://www.dovepress.com/a-silica-based-ph-sensitive-nanomatrix-system-improves-the-oral-absorp-a10998https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Wei Qu,1,2 Yong Li,2,* Lars Hovgaard,3 Song Li,1 Wenbin Dai,1 Jiancheng Wang,1 Xuan Zhang,1 Qiang Zhang1,1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, PR China; 2Department of Nutrition and Food Hygiene, Peking University Health Science Center, Beijing 100191, PR China; 3Oral Formulation Development, Novo Nordisk A/S, Maalov, DenmarkBoth authors contributed equally to this workBackground: Glucagon-like peptide-1 (GLP-1) (7&ndash;36) is a peptide incretin hormone released from the endocrine L-cells of the intestinal mucosa with unique antidiabetic potential. Due to low absorption efficiency and instability in the gastrointestinal tract, the introduction of orally active GLP-1 is a large challenge. Here we developed a novel silica-based pH-sensitive nanomatrix of GLP-1 (SPN-GLP-1) in order to provide a strategy for oral peptide delivery.Methods: SPN-GLP-1 composed of silica nanoparticles and pH-sensitive Eudragit&reg; was prepared and characterized by dynamic light scattering, scanning electron microscope, transmission electron microscope, high-performance liquid chromatography, surface analysis, drug release, and so on. Its permeability across the Caco-2 cell monolayer and intestinal mucosa, proteolytic stability against the intestinal enzymes, pharmacokinetics, hypoglycemic effect in the intraperitoneal glucose tolerance test (IPGTT), and primary toxicity were then evaluated.Results: It was indicated that the nanomatrix system obtained had a unique nanoscale structure and pH-sensitivity in drug release. It displayed a five-fold intestinal mucosa permeability and significantly higher proteolytic stability compared to native GLP-1 (P &lt; 0.001). A longer half-life was observed after oral administration of SPN-GLP-1, and its relative bioavailability was 35.67% in comparison to intraperitoneal GLP-1. Oral delivery of SPN-GLP-1 significantly reduced the blood glucose level and its hypoglycemic effect over intraperitoneal GLP-1 reached 77%. There was no evident toxicity of SPN-GLP-1 found from both animal status and histochemical analysis of gastrointestinal tissues.Conclusion: The silica-based pH-sensitive nanomatrix designed and prepared here might be considered as a potential oral delivery system not only for GLP-1, but also for other peptide or macromolecular drugs.Keywords: nanomatrix, oral peptide delivery, silicon nanoparticles, pH-sensitive, GLP-1Qu WLi YHovgaard LLi SDai WWang JZhang XZhang QDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 4983-4994 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Qu W Li Y Hovgaard L Li S Dai W Wang J Zhang X Zhang Q A silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-1
description	Wei Qu,1,2 Yong Li,2,* Lars Hovgaard,3 Song Li,1 Wenbin Dai,1 Jiancheng Wang,1 Xuan Zhang,1 Qiang Zhang1,1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, PR China; 2Department of Nutrition and Food Hygiene, Peking University Health Science Center, Beijing 100191, PR China; 3Oral Formulation Development, Novo Nordisk A/S, Maalov, DenmarkBoth authors contributed equally to this workBackground: Glucagon-like peptide-1 (GLP-1) (7&ndash;36) is a peptide incretin hormone released from the endocrine L-cells of the intestinal mucosa with unique antidiabetic potential. Due to low absorption efficiency and instability in the gastrointestinal tract, the introduction of orally active GLP-1 is a large challenge. Here we developed a novel silica-based pH-sensitive nanomatrix of GLP-1 (SPN-GLP-1) in order to provide a strategy for oral peptide delivery.Methods: SPN-GLP-1 composed of silica nanoparticles and pH-sensitive Eudragit&reg; was prepared and characterized by dynamic light scattering, scanning electron microscope, transmission electron microscope, high-performance liquid chromatography, surface analysis, drug release, and so on. Its permeability across the Caco-2 cell monolayer and intestinal mucosa, proteolytic stability against the intestinal enzymes, pharmacokinetics, hypoglycemic effect in the intraperitoneal glucose tolerance test (IPGTT), and primary toxicity were then evaluated.Results: It was indicated that the nanomatrix system obtained had a unique nanoscale structure and pH-sensitivity in drug release. It displayed a five-fold intestinal mucosa permeability and significantly higher proteolytic stability compared to native GLP-1 (P &lt; 0.001). A longer half-life was observed after oral administration of SPN-GLP-1, and its relative bioavailability was 35.67% in comparison to intraperitoneal GLP-1. Oral delivery of SPN-GLP-1 significantly reduced the blood glucose level and its hypoglycemic effect over intraperitoneal GLP-1 reached 77%. There was no evident toxicity of SPN-GLP-1 found from both animal status and histochemical analysis of gastrointestinal tissues.Conclusion: The silica-based pH-sensitive nanomatrix designed and prepared here might be considered as a potential oral delivery system not only for GLP-1, but also for other peptide or macromolecular drugs.Keywords: nanomatrix, oral peptide delivery, silicon nanoparticles, pH-sensitive, GLP-1
format	article
author	Qu W Li Y Hovgaard L Li S Dai W Wang J Zhang X Zhang Q
author_facet	Qu W Li Y Hovgaard L Li S Dai W Wang J Zhang X Zhang Q
author_sort	Qu W
title	A silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-1
title_short	A silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-1
title_full	A silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-1
title_fullStr	A silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-1
title_full_unstemmed	A silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-1
title_sort	silica-based ph-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-1
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/fbaae50d237841e6b552403156edff07
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A silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-1

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