Design and in vivo evaluation of an oral delivery system for insulin
To develop an oral controlled release system for insulin. The polymer-inhibitor conjugates carboxymethylcellulose (CMC)-Bowman-Birk inhibitor and CMC-elastatinal were homogenized with polycarbophil-cysteine conjugate, insulin, and mannitol, compressed to 2 mg microtablets and enteric coated with a p...
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| Veröffentlicht in: | Pharmaceutical research 2000-12, Vol.17 (12), p.1468-1474 |
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| creator | MARSCHÜTZ, Michaela K CALICETI, Paolo BERNKOP-SCHNÜRCH, Andreas |
| description | To develop an oral controlled release system for insulin.
The polymer-inhibitor conjugates carboxymethylcellulose (CMC)-Bowman-Birk inhibitor and CMC-elastatinal were homogenized with polycarbophil-cysteine conjugate, insulin, and mannitol, compressed to 2 mg microtablets and enteric coated with a polymethacrylate. The protective effect of this delivery system for insulin towards enzymatic degradation, as well as the release profile, was evaluated in vitro. In addition, the effect of the dosage form on glucose levels of diabetic mice was determined.
Tablets containing the CMC-inhibitor conjugates showed a strong protective effect for insulin. Whereas 91.6 +/- 7.4% (mean +/- SD, n = 3) of insulin in the dosage form without the inhibitor conjugates has been degraded within 3 h of incubation in an artificial intestinal fluid containing physiological concentrations of trypsin, chymotrypsin, and elastase, 49.7 +/- 5.5% (mean +/- SD, n = 3) of insulin remained stable in the delivery system containing the polymer-inhibitor conjugates. Additionally, polycarbophil-cysteine (PCP-Cys) provides high cohesiveness of the dosage form, due to the formation of interas well as intramolecular disulfide bonds within the polymer matrix. According to this, a controlled release of insulin could be achieved over a time period of 10 h. Furthermore, in vivo studies in diabetic mice showed a decrease in basal glucose levels of 20% to 40% during a time period of 80 h.
Mucoadhesive polymer-inhibitor conjugates might represent a promising excipient in delivery systems for oral (poly)peptide delivery. |
| doi_str_mv | 10.1023/A:1007696723125 |
| format | Article |
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The polymer-inhibitor conjugates carboxymethylcellulose (CMC)-Bowman-Birk inhibitor and CMC-elastatinal were homogenized with polycarbophil-cysteine conjugate, insulin, and mannitol, compressed to 2 mg microtablets and enteric coated with a polymethacrylate. The protective effect of this delivery system for insulin towards enzymatic degradation, as well as the release profile, was evaluated in vitro. In addition, the effect of the dosage form on glucose levels of diabetic mice was determined.
Tablets containing the CMC-inhibitor conjugates showed a strong protective effect for insulin. Whereas 91.6 +/- 7.4% (mean +/- SD, n = 3) of insulin in the dosage form without the inhibitor conjugates has been degraded within 3 h of incubation in an artificial intestinal fluid containing physiological concentrations of trypsin, chymotrypsin, and elastase, 49.7 +/- 5.5% (mean +/- SD, n = 3) of insulin remained stable in the delivery system containing the polymer-inhibitor conjugates. Additionally, polycarbophil-cysteine (PCP-Cys) provides high cohesiveness of the dosage form, due to the formation of interas well as intramolecular disulfide bonds within the polymer matrix. According to this, a controlled release of insulin could be achieved over a time period of 10 h. Furthermore, in vivo studies in diabetic mice showed a decrease in basal glucose levels of 20% to 40% during a time period of 80 h.
Mucoadhesive polymer-inhibitor conjugates might represent a promising excipient in delivery systems for oral (poly)peptide delivery.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/A:1007696723125</identifier><identifier>PMID: 11303955</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Acids ; Acrylic Resins ; Animals ; Bioavailability ; Biological and medical sciences ; Carboxymethylcellulose Sodium ; Carboxypeptidase B ; Carboxypeptidases - chemistry ; Carboxypeptidases A ; Cysteine ; Diabetes ; Diabetes Mellitus, Experimental - blood ; Diabetes Mellitus, Experimental - drug therapy ; Dosage Forms ; Drug Carriers ; Drug Delivery Systems ; Drug dosages ; Enzymes ; General and cellular metabolism. Vitamins ; General pharmacology ; Hypoglycemic Agents - administration & dosage ; Hypoglycemic Agents - blood ; Hypoglycemic Agents - therapeutic use ; Insulin ; Insulin - administration & dosage ; Insulin - blood ; Insulin - therapeutic use ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Oral administration ; Pharmaceutic Aids ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Physiology ; Polymers</subject><ispartof>Pharmaceutical research, 2000-12, Vol.17 (12), p.1468-1474</ispartof><rights>2001 INIST-CNRS</rights><rights>Copyright Kluwer Academic Publishers Dec 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=937929$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11303955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MARSCHÜTZ, Michaela K</creatorcontrib><creatorcontrib>CALICETI, Paolo</creatorcontrib><creatorcontrib>BERNKOP-SCHNÜRCH, Andreas</creatorcontrib><title>Design and in vivo evaluation of an oral delivery system for insulin</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>To develop an oral controlled release system for insulin.
The polymer-inhibitor conjugates carboxymethylcellulose (CMC)-Bowman-Birk inhibitor and CMC-elastatinal were homogenized with polycarbophil-cysteine conjugate, insulin, and mannitol, compressed to 2 mg microtablets and enteric coated with a polymethacrylate. The protective effect of this delivery system for insulin towards enzymatic degradation, as well as the release profile, was evaluated in vitro. In addition, the effect of the dosage form on glucose levels of diabetic mice was determined.
Tablets containing the CMC-inhibitor conjugates showed a strong protective effect for insulin. Whereas 91.6 +/- 7.4% (mean +/- SD, n = 3) of insulin in the dosage form without the inhibitor conjugates has been degraded within 3 h of incubation in an artificial intestinal fluid containing physiological concentrations of trypsin, chymotrypsin, and elastase, 49.7 +/- 5.5% (mean +/- SD, n = 3) of insulin remained stable in the delivery system containing the polymer-inhibitor conjugates. Additionally, polycarbophil-cysteine (PCP-Cys) provides high cohesiveness of the dosage form, due to the formation of interas well as intramolecular disulfide bonds within the polymer matrix. According to this, a controlled release of insulin could be achieved over a time period of 10 h. Furthermore, in vivo studies in diabetic mice showed a decrease in basal glucose levels of 20% to 40% during a time period of 80 h.
Mucoadhesive polymer-inhibitor conjugates might represent a promising excipient in delivery systems for oral (poly)peptide delivery.</description><subject>Acids</subject><subject>Acrylic Resins</subject><subject>Animals</subject><subject>Bioavailability</subject><subject>Biological and medical sciences</subject><subject>Carboxymethylcellulose Sodium</subject><subject>Carboxypeptidase B</subject><subject>Carboxypeptidases - chemistry</subject><subject>Carboxypeptidases A</subject><subject>Cysteine</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Experimental - blood</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Dosage Forms</subject><subject>Drug Carriers</subject><subject>Drug Delivery Systems</subject><subject>Drug dosages</subject><subject>Enzymes</subject><subject>General and cellular metabolism. Vitamins</subject><subject>General pharmacology</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Hypoglycemic Agents - blood</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Insulin</subject><subject>Insulin - administration & dosage</subject><subject>Insulin - blood</subject><subject>Insulin - therapeutic use</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Oral administration</subject><subject>Pharmaceutic Aids</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Physiology</subject><subject>Polymers</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpd0E1LxDAQBuAgiruunr1JUPBWTSZtPrwt6ycseFHwVtI0lSxpsyZtYf-9BVcPnuYwzzsML0LnlNxQAux2eUcJEVxxAYxCcYDmtBAsUyT_OERzIiDPpMjpDJ2ktCGESKryYzSjlBGmimKO7u9tcp8d1l2NXYdHNwZsR-0H3bvQ4dBMGxyi9ri23o027nDapd62uAlxSqTBu-4UHTXaJ3u2nwv0_vjwtnrO1q9PL6vlOtsChz6rQEquuVGccdvkQFgtDZeUMaUtFZyB1XVVA9RQGarAMiZpXlWmMkJI2bAFuv65u43ha7CpL1uXjPVedzYMqRRQSCmYnODlP7gJQ-ym30oA4AWdOpvQxR4NVWvrchtdq-Ou_C1nAld7oJPRvom6My79OcWEAsW-AZ4PcW8</recordid><startdate>20001201</startdate><enddate>20001201</enddate><creator>MARSCHÜTZ, Michaela K</creator><creator>CALICETI, Paolo</creator><creator>BERNKOP-SCHNÜRCH, Andreas</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20001201</creationdate><title>Design and in vivo evaluation of an oral delivery system for insulin</title><author>MARSCHÜTZ, Michaela K ; CALICETI, Paolo ; BERNKOP-SCHNÜRCH, Andreas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p262t-b2886a6c9636ef4203d8c681339ae17632eadbd22d2bc192e33814bbcbc7788f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Acids</topic><topic>Acrylic Resins</topic><topic>Animals</topic><topic>Bioavailability</topic><topic>Biological and medical sciences</topic><topic>Carboxymethylcellulose Sodium</topic><topic>Carboxypeptidase B</topic><topic>Carboxypeptidases - chemistry</topic><topic>Carboxypeptidases A</topic><topic>Cysteine</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Experimental - blood</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Dosage Forms</topic><topic>Drug Carriers</topic><topic>Drug Delivery Systems</topic><topic>Drug dosages</topic><topic>Enzymes</topic><topic>General and cellular metabolism. Vitamins</topic><topic>General pharmacology</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Hypoglycemic Agents - blood</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Insulin</topic><topic>Insulin - administration & dosage</topic><topic>Insulin - blood</topic><topic>Insulin - therapeutic use</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Oral administration</topic><topic>Pharmaceutic Aids</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Physiology</topic><topic>Polymers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MARSCHÜTZ, Michaela K</creatorcontrib><creatorcontrib>CALICETI, Paolo</creatorcontrib><creatorcontrib>BERNKOP-SCHNÜRCH, Andreas</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MARSCHÜTZ, Michaela K</au><au>CALICETI, Paolo</au><au>BERNKOP-SCHNÜRCH, Andreas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design and in vivo evaluation of an oral delivery system for insulin</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2000-12-01</date><risdate>2000</risdate><volume>17</volume><issue>12</issue><spage>1468</spage><epage>1474</epage><pages>1468-1474</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>To develop an oral controlled release system for insulin.
The polymer-inhibitor conjugates carboxymethylcellulose (CMC)-Bowman-Birk inhibitor and CMC-elastatinal were homogenized with polycarbophil-cysteine conjugate, insulin, and mannitol, compressed to 2 mg microtablets and enteric coated with a polymethacrylate. The protective effect of this delivery system for insulin towards enzymatic degradation, as well as the release profile, was evaluated in vitro. In addition, the effect of the dosage form on glucose levels of diabetic mice was determined.
Tablets containing the CMC-inhibitor conjugates showed a strong protective effect for insulin. Whereas 91.6 +/- 7.4% (mean +/- SD, n = 3) of insulin in the dosage form without the inhibitor conjugates has been degraded within 3 h of incubation in an artificial intestinal fluid containing physiological concentrations of trypsin, chymotrypsin, and elastase, 49.7 +/- 5.5% (mean +/- SD, n = 3) of insulin remained stable in the delivery system containing the polymer-inhibitor conjugates. Additionally, polycarbophil-cysteine (PCP-Cys) provides high cohesiveness of the dosage form, due to the formation of interas well as intramolecular disulfide bonds within the polymer matrix. According to this, a controlled release of insulin could be achieved over a time period of 10 h. Furthermore, in vivo studies in diabetic mice showed a decrease in basal glucose levels of 20% to 40% during a time period of 80 h.
Mucoadhesive polymer-inhibitor conjugates might represent a promising excipient in delivery systems for oral (poly)peptide delivery.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>11303955</pmid><doi>10.1023/A:1007696723125</doi><tpages>7</tpages></addata></record> |
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| subjects | Acids Acrylic Resins Animals Bioavailability Biological and medical sciences Carboxymethylcellulose Sodium Carboxypeptidase B Carboxypeptidases - chemistry Carboxypeptidases A Cysteine Diabetes Diabetes Mellitus, Experimental - blood Diabetes Mellitus, Experimental - drug therapy Dosage Forms Drug Carriers Drug Delivery Systems Drug dosages Enzymes General and cellular metabolism. Vitamins General pharmacology Hypoglycemic Agents - administration & dosage Hypoglycemic Agents - blood Hypoglycemic Agents - therapeutic use Insulin Insulin - administration & dosage Insulin - blood Insulin - therapeutic use Medical sciences Mice Mice, Inbred BALB C Oral administration Pharmaceutic Aids Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Physiology Polymers |
| title | Design and in vivo evaluation of an oral delivery system for insulin |
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