| Facilitated nanoscale delivery of insulin across intestinal membrane models. | |
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MedLine Citation:
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PMID: 21501675 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The effect of nanoparticulate delivery system on enhancing insulin permeation through intestinal membrane was evaluated in different intestinal epithelial models using cell cultures and excised intestinal tissues. Multilayered nanoparticles were formulated by encapsulating insulin within a core consisting of alginate and dextran sulfate nucleating around calcium and binding to poloxamer, stabilized by chitosan, and subsequently coated with albumin. Insulin permeation through Caco-2 cell monolayer was enhanced 2.1-fold, facilitated by the nanoparticles compared with insulin alone, 3.7-fold through a mucus-secreting Caco-2/HT29 co-culture, and 3.9-fold through excised intestinal mucosa of Wistar rats. Correlation of Caco-2/HT29 co-culture cells with the animal-model intestinal membrane demonstrates that the mucus layer plays a significant role in determining the effectiveness of oral nanoformulations in delivering poorly absorbed drugs. Albumin was applied to the nanoparticles as outermost coat to protect insulin through shielding from proteolytic degradation. The effect of the albumin layering on insulin permeation was compared with albumin-free nanoparticles that mimic the result of albumin being enzymatically removed during gastric and intestinal transport. Results showed that albumin layering is important toward improving insulin transport across the intestinal membrane, possibly by stabilizing insulin in the intestinal conditions. Transcellular permeation was evidenced by internalization of independently labeled insulin and nanoparticles into enterocytes, in which insulin appeared to remain associated with the nanoparticles. Transcellular transport of insulin through rat intestinal mucosa may represent the predominant mechanism by which nanoparticles facilitate insulin permeation. Nanoformulations demonstrated biocompatibility with rat intestinal mucosa through determination of cell viability via monitoring of mitochondrial dehydrogenases. Insulin permeation facilitated by the biocompatible nanoparticles suggests a potential carrier system in delivering protein-based drugs by the oral route. |
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Authors:
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Camile B Woitiski; Bruno Sarmento; Rui A Carvalho; Ronald J Neufeld; Francisco Veiga |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-8 |
Journal Detail:
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Title: International journal of pharmaceutics Volume: - ISSN: 1873-3476 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7804127 Medline TA: Int J Pharm Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Center for Pharmaceutical Studies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; Chemical Engineering Department, Queen's University, Kingston, Ontario K7L 3N6, Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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