DC Field | Value | Language |
---|---|---|
dc.contributor.author | Ahn, Sukyung | ko |
dc.contributor.author | Lee, In-Hyun | ko |
dc.contributor.author | Lee, Eunhye | ko |
dc.contributor.author | Kim, Hyungjun | ko |
dc.contributor.author | Kim, Yong-Chul | ko |
dc.contributor.author | Jon, Sangyong | ko |
dc.date.accessioned | 2013-08-22T02:28:28Z | - |
dc.date.available | 2013-08-22T02:28:28Z | - |
dc.date.created | 2013-08-21 | - |
dc.date.created | 2013-08-21 | - |
dc.date.issued | 2013-09 | - |
dc.identifier.citation | JOURNAL OF CONTROLLED RELEASE, v.170, no.2, pp.226 - 232 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.uri | http://hdl.handle.net/10203/175542 | - |
dc.description.abstract | Despite the therapeutic potential of exendin-4 as a glucagon-like peptide-1 (GLP-1) mimetic for the treatment of type 2 diabetes, its utility has so far been limited because of the low level of patient compliance due to the requirement for frequent injections. In this study, an orally available exendin-4 was produced by conjugating it to low molecular weight chitosan (LMWC). Conjugation between the LMWC and cysteinylated exendin-4 was carried out using a cleavable linker system in order to maximize the availability of the active peptide. The LMWC-exendin-4 conjugate formed a nanoparticle structure with a mean particle size of 101 +/- 41 nm through complexation between the positively charged LMWC backbone and the negatively charged exendin-4 of individual conjugate molecules. The biological activity of the LMWC-exendin-4 conjugatewas evaluated in an INS-1 cell line. The LMWC-exendin-4 conjugate stimulated insulin secretion in a dose dependent manner as similar as that of native exendin-4. From the pharmacokinetic study after oral administration of the conjugate, a C-max value of 344 pg/mL and a T-max of 6 h were observed, and the bioavailability, relative to the subcutaneous counterpart, was found to be 6.4%. Furthermore, the absorbed exendin-4 demonstrated a significantly enhanced hypoglycemic effect. These results suggest that the LMWC-exendin-4 conjugate could be used as a potential oral antidiabetic agent for the treatment of type 2 diabetes. (C) 2013 Elsevier B. V. All rights reserved. | - |
dc.language | English | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.subject | GLUCAGON-LIKE PEPTIDE-1 | - |
dc.subject | ABSORPTION ENHANCEMENT | - |
dc.subject | INSULIN DELIVERY | - |
dc.subject | NANOPARTICLES | - |
dc.subject | MECHANISM | - |
dc.subject | PROTEIN | - |
dc.subject | EXENDIN-4 | - |
dc.subject | ANALOGS | - |
dc.subject | SYSTEMS | - |
dc.subject | PHARMACOKINETICS | - |
dc.title | Oral delivery of an anti-diabetic peptide drug via conjugation and complexation with low molecular weight chitosan | - |
dc.type | Article | - |
dc.identifier.wosid | 000321747200009 | - |
dc.identifier.scopusid | 2-s2.0-84879468609 | - |
dc.type.rims | ART | - |
dc.citation.volume | 170 | - |
dc.citation.issue | 2 | - |
dc.citation.beginningpage | 226 | - |
dc.citation.endingpage | 232 | - |
dc.citation.publicationname | JOURNAL OF CONTROLLED RELEASE | - |
dc.identifier.doi | 10.1016/j.jconrel.2013.05.031 | - |
dc.contributor.localauthor | Jon, Sangyong | - |
dc.contributor.nonIdAuthor | Ahn, Sukyung | - |
dc.contributor.nonIdAuthor | Lee, In-Hyun | - |
dc.contributor.nonIdAuthor | Lee, Eunhye | - |
dc.contributor.nonIdAuthor | Kim, Hyungjun | - |
dc.contributor.nonIdAuthor | Kim, Yong-Chul | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Oral delivery | - |
dc.subject.keywordAuthor | Peptides | - |
dc.subject.keywordAuthor | Chitosan | - |
dc.subject.keywordAuthor | Exendin-4 | - |
dc.subject.keywordAuthor | Conjugates | - |
dc.subject.keywordAuthor | Type 2 diabetes | - |
dc.subject.keywordPlus | GLUCAGON-LIKE PEPTIDE-1 | - |
dc.subject.keywordPlus | ABSORPTION ENHANCEMENT | - |
dc.subject.keywordPlus | INSULIN DELIVERY | - |
dc.subject.keywordPlus | NANOPARTICLES | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | EXENDIN-4 | - |
dc.subject.keywordPlus | ANALOGS | - |
dc.subject.keywordPlus | SYSTEMS | - |
dc.subject.keywordPlus | PHARMACOKINETICS | - |
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