Starch Microspheres Induce Pulsatile Delivery of Drugs and Peptides Across the Epithelial Barrier by Reversible Separation of the Tight Junctions
Abstract Non-parenteral administration of peptide drugs is prevented by the limited permeability of the epithelia lining the mucosal tissues. As a new approach to non-parenteral delivery, degradable starch microspheres (dsm) were coated with insulin and administered to the mucosal side of monolayers...
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| Veröffentlicht in: | Journal of drug targeting 1995, Vol.2 (6), p.501-507 |
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| container_issue | 6 |
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| container_title | Journal of drug targeting |
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| creator | Björk, Erik Isaksson, Ulrika Edman, Peter Artursson, Per |
| description | Abstract
Non-parenteral administration of peptide drugs is prevented by the limited permeability of the epithelia lining the mucosal tissues. As a new approach to non-parenteral delivery, degradable starch microspheres (dsm) were coated with insulin and administered to the mucosal side of monolayers of human intestinal epithelial (Caco-2) cells in vitro. The microspheres induced a pulsed delivery of insulin across the epithelium that lasted for 1-2 h. The pulsed delivery correlated with a reversible appearance of focal dilatations in the tight junctions between the epithelial cells, indicating that dsm enhance the delivery of insulin by the paracellular route. These results provide an explanation for the previously observed absorption enhancing properties of dsm. |
| doi_str_mv | 10.3109/10611869509015920 |
| format | Article |
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Non-parenteral administration of peptide drugs is prevented by the limited permeability of the epithelia lining the mucosal tissues. As a new approach to non-parenteral delivery, degradable starch microspheres (dsm) were coated with insulin and administered to the mucosal side of monolayers of human intestinal epithelial (Caco-2) cells in vitro. The microspheres induced a pulsed delivery of insulin across the epithelium that lasted for 1-2 h. The pulsed delivery correlated with a reversible appearance of focal dilatations in the tight junctions between the epithelial cells, indicating that dsm enhance the delivery of insulin by the paracellular route. These results provide an explanation for the previously observed absorption enhancing properties of dsm.</description><identifier>ISSN: 1061-186X</identifier><identifier>EISSN: 1029-2330</identifier><identifier>DOI: 10.3109/10611869509015920</identifier><identifier>PMID: 7773612</identifier><language>eng</language><publisher>England: Informa UK Ltd</publisher><subject>Absorption enhancement ; Analysis of Variance ; Biological Transport - drug effects ; Caco-2 ; Carcinoma - pathology ; Chi-Square Distribution ; Colorectal Neoplasms - pathology ; Dose-Response Relationship, Drug ; Drug Delivery Systems ; Drug transport ; Epithelial Cells ; Epithelium - drug effects ; Epithelium - metabolism ; Humans ; Insulin - administration & dosage ; Insulin - pharmacokinetics ; Insulin - pharmacology ; Intercellular Junctions - drug effects ; Intercellular Junctions - physiology ; Intestinal Absorption - drug effects ; Intestinal epithelium ; Intestines - cytology ; Intestines - drug effects ; Intestines - metabolism ; Mannitol - administration & dosage ; Mannitol - pharmacokinetics ; Mannitol - pharmacology ; Microscopy, Fluorescence ; Microspheres ; Permeability - drug effects ; Pulsatile Flow - drug effects ; Starch - chemistry ; Starch - metabolism ; Starch - pharmacology ; Tight Junction ; Tumor Cells, Cultured</subject><ispartof>Journal of drug targeting, 1995, Vol.2 (6), p.501-507</ispartof><rights>1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 1995</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-294d111c8b34dbe135df365d04dba10172902b8d9aae4fb40da416f2954a35b93</citedby><cites>FETCH-LOGICAL-c496t-294d111c8b34dbe135df365d04dba10172902b8d9aae4fb40da416f2954a35b93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.3109/10611869509015920$$EPDF$$P50$$Ginformahealthcare$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.3109/10611869509015920$$EHTML$$P50$$Ginformahealthcare$$H</linktohtml><link.rule.ids>314,780,784,4024,27923,27924,27925,59647,59753,60436,60542,61221,61256,61402,61437</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7773612$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Björk, Erik</creatorcontrib><creatorcontrib>Isaksson, Ulrika</creatorcontrib><creatorcontrib>Edman, Peter</creatorcontrib><creatorcontrib>Artursson, Per</creatorcontrib><title>Starch Microspheres Induce Pulsatile Delivery of Drugs and Peptides Across the Epithelial Barrier by Reversible Separation of the Tight Junctions</title><title>Journal of drug targeting</title><addtitle>J Drug Target</addtitle><description>Abstract
Non-parenteral administration of peptide drugs is prevented by the limited permeability of the epithelia lining the mucosal tissues. As a new approach to non-parenteral delivery, degradable starch microspheres (dsm) were coated with insulin and administered to the mucosal side of monolayers of human intestinal epithelial (Caco-2) cells in vitro. The microspheres induced a pulsed delivery of insulin across the epithelium that lasted for 1-2 h. The pulsed delivery correlated with a reversible appearance of focal dilatations in the tight junctions between the epithelial cells, indicating that dsm enhance the delivery of insulin by the paracellular route. These results provide an explanation for the previously observed absorption enhancing properties of dsm.</description><subject>Absorption enhancement</subject><subject>Analysis of Variance</subject><subject>Biological Transport - drug effects</subject><subject>Caco-2</subject><subject>Carcinoma - pathology</subject><subject>Chi-Square Distribution</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Delivery Systems</subject><subject>Drug transport</subject><subject>Epithelial Cells</subject><subject>Epithelium - drug effects</subject><subject>Epithelium - metabolism</subject><subject>Humans</subject><subject>Insulin - administration & dosage</subject><subject>Insulin - pharmacokinetics</subject><subject>Insulin - pharmacology</subject><subject>Intercellular Junctions - drug effects</subject><subject>Intercellular Junctions - physiology</subject><subject>Intestinal Absorption - drug effects</subject><subject>Intestinal epithelium</subject><subject>Intestines - cytology</subject><subject>Intestines - drug effects</subject><subject>Intestines - metabolism</subject><subject>Mannitol - administration & dosage</subject><subject>Mannitol - pharmacokinetics</subject><subject>Mannitol - pharmacology</subject><subject>Microscopy, Fluorescence</subject><subject>Microspheres</subject><subject>Permeability - drug effects</subject><subject>Pulsatile Flow - drug effects</subject><subject>Starch - chemistry</subject><subject>Starch - metabolism</subject><subject>Starch - pharmacology</subject><subject>Tight Junction</subject><subject>Tumor Cells, Cultured</subject><issn>1061-186X</issn><issn>1029-2330</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9u1DAQxi0EKqXwAByQfOIW8MRJdi249B9QVERFi8QtmtiTxpU3CeMEtI_BG-OwKySE4DRjz_f9ZH8jxFNQLzQo8xJUBbCuTKmMgtLk6p44BJWbLNda3V_6CrIk-PJQPIrxTinQFagDcbBarVKXH4of1xOy7eQHb3mIY0dMUV70brYkr-YQcfKB5BkF_414K4dWnvF8GyX2Tl7ROHmX9MeLN8qpI3k--lSCxyBPkNkTy2YrP1FyR98k1DWNyIk69Atssdz4226S7-feLrfxsXjQYoj0ZF-PxOc35zen77LLj28vTo8vM1uYaspyUzgAsOtGF64h0KVrdVU6lU4ICla5UXmzdgaRirYplMMCqjY3ZYG6bIw-Es933JGHrzPFqd74aCkE7GmYY50SShC9CGEn_PVLprYe2W-QtzWoellD_dcakufZHj43G3K_Hfvc0_z1bu77duANfh84uHrCbRi4Zeytjwv63_hXf9g7wjB1Fpnqu2HmPuX2n8f9BCLTqe8</recordid><startdate>1995</startdate><enddate>1995</enddate><creator>Björk, Erik</creator><creator>Isaksson, Ulrika</creator><creator>Edman, Peter</creator><creator>Artursson, Per</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>1995</creationdate><title>Starch Microspheres Induce Pulsatile Delivery of Drugs and Peptides Across the Epithelial Barrier by Reversible Separation of the Tight Junctions</title><author>Björk, Erik ; Isaksson, Ulrika ; Edman, Peter ; Artursson, Per</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-294d111c8b34dbe135df365d04dba10172902b8d9aae4fb40da416f2954a35b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Absorption enhancement</topic><topic>Analysis of Variance</topic><topic>Biological Transport - drug effects</topic><topic>Caco-2</topic><topic>Carcinoma - pathology</topic><topic>Chi-Square Distribution</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Delivery Systems</topic><topic>Drug transport</topic><topic>Epithelial Cells</topic><topic>Epithelium - drug effects</topic><topic>Epithelium - metabolism</topic><topic>Humans</topic><topic>Insulin - administration & dosage</topic><topic>Insulin - pharmacokinetics</topic><topic>Insulin - pharmacology</topic><topic>Intercellular Junctions - drug effects</topic><topic>Intercellular Junctions - physiology</topic><topic>Intestinal Absorption - drug effects</topic><topic>Intestinal epithelium</topic><topic>Intestines - cytology</topic><topic>Intestines - drug effects</topic><topic>Intestines - metabolism</topic><topic>Mannitol - administration & dosage</topic><topic>Mannitol - pharmacokinetics</topic><topic>Mannitol - pharmacology</topic><topic>Microscopy, Fluorescence</topic><topic>Microspheres</topic><topic>Permeability - drug effects</topic><topic>Pulsatile Flow - drug effects</topic><topic>Starch - chemistry</topic><topic>Starch - metabolism</topic><topic>Starch - pharmacology</topic><topic>Tight Junction</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Björk, Erik</creatorcontrib><creatorcontrib>Isaksson, Ulrika</creatorcontrib><creatorcontrib>Edman, Peter</creatorcontrib><creatorcontrib>Artursson, Per</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of drug targeting</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Björk, Erik</au><au>Isaksson, Ulrika</au><au>Edman, Peter</au><au>Artursson, Per</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Starch Microspheres Induce Pulsatile Delivery of Drugs and Peptides Across the Epithelial Barrier by Reversible Separation of the Tight Junctions</atitle><jtitle>Journal of drug targeting</jtitle><addtitle>J Drug Target</addtitle><date>1995</date><risdate>1995</risdate><volume>2</volume><issue>6</issue><spage>501</spage><epage>507</epage><pages>501-507</pages><issn>1061-186X</issn><eissn>1029-2330</eissn><abstract>Abstract
Non-parenteral administration of peptide drugs is prevented by the limited permeability of the epithelia lining the mucosal tissues. As a new approach to non-parenteral delivery, degradable starch microspheres (dsm) were coated with insulin and administered to the mucosal side of monolayers of human intestinal epithelial (Caco-2) cells in vitro. The microspheres induced a pulsed delivery of insulin across the epithelium that lasted for 1-2 h. The pulsed delivery correlated with a reversible appearance of focal dilatations in the tight junctions between the epithelial cells, indicating that dsm enhance the delivery of insulin by the paracellular route. These results provide an explanation for the previously observed absorption enhancing properties of dsm.</abstract><cop>England</cop><pub>Informa UK Ltd</pub><pmid>7773612</pmid><doi>10.3109/10611869509015920</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Journal of drug targeting, 1995, Vol.2 (6), p.501-507 |
| issn | 1061-186X 1029-2330 |
| language | eng |
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| source | MEDLINE; Taylor & Francis:Master (3349 titles); Taylor & Francis Medical Library - CRKN |
| subjects | Absorption enhancement Analysis of Variance Biological Transport - drug effects Caco-2 Carcinoma - pathology Chi-Square Distribution Colorectal Neoplasms - pathology Dose-Response Relationship, Drug Drug Delivery Systems Drug transport Epithelial Cells Epithelium - drug effects Epithelium - metabolism Humans Insulin - administration & dosage Insulin - pharmacokinetics Insulin - pharmacology Intercellular Junctions - drug effects Intercellular Junctions - physiology Intestinal Absorption - drug effects Intestinal epithelium Intestines - cytology Intestines - drug effects Intestines - metabolism Mannitol - administration & dosage Mannitol - pharmacokinetics Mannitol - pharmacology Microscopy, Fluorescence Microspheres Permeability - drug effects Pulsatile Flow - drug effects Starch - chemistry Starch - metabolism Starch - pharmacology Tight Junction Tumor Cells, Cultured |
| title | Starch Microspheres Induce Pulsatile Delivery of Drugs and Peptides Across the Epithelial Barrier by Reversible Separation of the Tight Junctions |
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