1 Ocak 2021 Dergi makalesi Açık Erişim

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

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    "creators": [
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        "name": "Celik-Tekeli, Merve"
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      {
        "name": "Celebi, Nevin"
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      {
        "affiliation": "Erciyes Univ, Fac Vet Med, Dept Pharmacol & Toxicol, TR-38238 Kayseri, Turkey", 
        "name": "Tekeli, M. Yasin"
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      {
        "affiliation": "Erciyes Univ, Fac Pharm, Dept Pharmaceut Technol, TR-38238 Kayseri, Turkey", 
        "name": "Aktas, Yesim"
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    "description": "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.", 
    "doi": "10.1016/j.ejps.2020.105644", 
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    "journal": {
      "title": "EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES", 
      "volume": "158"
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    "license": {
      "id": "cc-by"
    }, 
    "publication_date": "2021-01-01", 
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    "title": "Evaluation of the hypoglycemic effect of exendin-4's new oral self-nanoemulsifying system in rats"
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