1 Ocak 2021 Dergi makalesi Açık Erişim

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

Citation Style Language JSON

{
  "DOI": "10.1016/j.ejps.2020.105644", 
  "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.", 
  "author": [
    {
      "family": "Celik-Tekeli", 
      "given": " Merve"
    }, 
    {
      "family": "Celebi", 
      "given": " Nevin"
    }, 
    {
      "family": "Tekeli", 
      "given": " M. Yasin"
    }, 
    {
      "family": "Aktas", 
      "given": " Yesim"
    }
  ], 
  "container_title": "EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES", 
  "id": "233606", 
  "issued": {
    "date-parts": [
      [
        2021, 
        1, 
        1
      ]
    ]
  }, 
  "title": "Evaluation of the hypoglycemic effect of exendin-4's new oral self-nanoemulsifying system in rats", 
  "type": "article-journal", 
  "volume": "158"
}