Evaluation of the hypoglycemic effect of exendin-4's new oral self-nanoemulsifying system in rats
Copyright © 2020 Elsevier B.V. All rights reserved..
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®/Labrasol® 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°C ± 3°C and at 25°C ± 60% RH for 12 months. Exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying systems increased AUC and Cmax values in non-diabetic rats compared to the oral exendin-4 solution. In diabetic rats, exendin-4/chymostatin loaded self nanoemulsifying systems increased Cmax values compared to the exendin-4 solution. Exendin-4/chymostatin loaded self-nanoemulsifying system decreased inter-subject variability compared to commercial Byetta®. At 30th minute after administration of exendin-4 loaded self-nanoemulsifying system, exendin-4/chymostatin loaded self nanoemulsifying system and Byetta®, blood glucose levels decreased to 23%, 25%, 29%, respectively. It has been shown that pharmacodynamic response is close to Byetta® 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:158 |
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| Enthalten in: |
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences - 158(2021) vom: 01. März, Seite 105644 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Celik-Tekeli, Merve [VerfasserIn] |
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| Links: |
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| Themen: |
9P1872D4OL |
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| Anmerkungen: |
Date Completed 21.06.2021 Date Revised 21.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejps.2020.105644 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM317649337 |
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| 245 | 1 | 0 | |a Evaluation of the hypoglycemic effect of exendin-4's new oral self-nanoemulsifying system in rats |
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| 520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
| 520 | |a 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®/Labrasol® 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°C ± 3°C and at 25°C ± 60% RH for 12 months. Exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying systems increased AUC and Cmax values in non-diabetic rats compared to the oral exendin-4 solution. In diabetic rats, exendin-4/chymostatin loaded self nanoemulsifying systems increased Cmax values compared to the exendin-4 solution. Exendin-4/chymostatin loaded self-nanoemulsifying system decreased inter-subject variability compared to commercial Byetta®. At 30th minute after administration of exendin-4 loaded self-nanoemulsifying system, exendin-4/chymostatin loaded self nanoemulsifying system and Byetta®, blood glucose levels decreased to 23%, 25%, 29%, respectively. It has been shown that pharmacodynamic response is close to Byetta® 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Exendin-4 | |
| 650 | 4 | |a Oral peptide delivery | |
| 650 | 4 | |a Pharmacodynamics | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 4 | |a Self-nanoemulsifying system | |
| 650 | 7 | |a Emulsions |2 NLM | |
| 650 | 7 | |a Hypoglycemic Agents |2 NLM | |
| 650 | 7 | |a Surface-Active Agents |2 NLM | |
| 650 | 7 | |a Exenatide |2 NLM | |
| 650 | 7 | |a 9P1872D4OL |2 NLM | |
| 700 | 1 | |a Celebi, Nevin |e verfasserin |4 aut | |
| 700 | 1 | |a Tekeli, M Yasin |e verfasserin |4 aut | |
| 700 | 1 | |a Aktas, Yesim |e verfasserin |4 aut | |
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