1 Ocak 2021 Dergi makalesi Açık Erişim

Celik-Tekeli, Merve; Celebi, Nevin; Tekeli, M. Yasin; Aktas, Yesim

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/233606</identifier>
  <creators>
    <creator>
      <creatorName>Celik-Tekeli, Merve</creatorName>
      <givenName>Merve</givenName>
      <familyName>Celik-Tekeli</familyName>
    </creator>
    <creator>
      <creatorName>Celebi, Nevin</creatorName>
      <givenName>Nevin</givenName>
      <familyName>Celebi</familyName>
    </creator>
    <creator>
      <creatorName>Tekeli, M. Yasin</creatorName>
      <givenName>M. Yasin</givenName>
      <familyName>Tekeli</familyName>
      <affiliation>Erciyes Univ, Fac Vet Med, Dept Pharmacol &amp; Toxicol, TR-38238 Kayseri, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Aktas, Yesim</creatorName>
      <givenName>Yesim</givenName>
      <familyName>Aktas</familyName>
      <affiliation>Erciyes Univ, Fac Pharm, Dept Pharmaceut Technol, TR-38238 Kayseri, Turkey</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Evaluation Of The Hypoglycemic Effect Of Exendin-4'S New Oral Self-Nanoemulsifying System In Rats</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2021</publicationYear>
  <dates>
    <date dateType="Issued">2021-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/233606</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.ejps.2020.105644</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">The objective of this study is to develop a new self-nanoemulsifying system containing exendin-4 with or without enzyme inhibitor chymostatin and to evaluate the effects of oral administration of exendin-4 and exendin-4/chymostatin loaded self nanoemulsifying system on plasma exendin-4, plasma insulin, blood glucose levels and to compare with the oral and subcutaneous administration of exendin-4 in non-diabetic and streptozotocin-induced type 2 diabetic rats. Exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying system containing ethyl oleate as the oil phase, Cremophor EL (R)/Labrasol (R) as the surfactants and propylene glycol as the co-solvent were prepared. The mean droplet size, polydispersity index, zeta potential and viscosity of exendin-4 loaded self-nanoemulsifying system were found as 24.28 +/- 0.43 nm, 0.17 +/- 0.01, -1.28 +/- 3.61 mV, 79.60 +/- 3.30 m.Pas, respectively. The mean droplet size, polydispersity index, zeta potential and viscosity of exendin-4/chymostatin loaded self-nanoemulsifying system were found as 20.25 +/- 0.35 nm, 0.11 +/- 0.02, -1.85 +/- 2.49 mV, 100.02 +/- 7.65 m.Pas, respectively according to our previous study. In the present study, we focused on long-term physical stability studies, pharmacokinetic studies and pharmacodynamic studies of prepared self-nanoemulsifying systems. According to the long-term physical stability data, exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying systems were found stable both at 5 degrees C +/- 3 degrees C and at 25 degrees C +/- 60% RH for 12 months. Exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying systems increased AUC and C-max values in non-diabetic rats compared to the oral exendin-4 solution. In diabetic rats, exendin-4/chymostatin loaded self nanoemulsifying systems increased C-max values compared to the exendin-4 solution. Exendin-4/chymostatin loaded self-nanoemulsifying system decreased inter-subject variability compared to commercial Byetta (R). At 30th minute after administration of exendin-4 loaded self-nanoemulsifying system, exendin-4/chymostatin loaded self nanoemulsifying system and Byetta (R), blood glucose levels decreased to 23%, 25%, 29%, respectively. It has been shown that pharmacodynamic response is close to Byetta (R) with exendin-4/chymostatin self-nanoemulsifying system oral administration. In conclusion, a self nanoemulsifying system was found to be a suitable carrier system, and the combination with enzyme inhibitor chymostatin is thought to be promising for oral delivery of exendin-4.</description>
  </descriptions>
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