Intramuscular injection of palmitic acid-conjugated Exendin-4 loaded multivesicular liposomes for long-acting and improving in-situ stability
BACKGROUND: Exendin-4 (Ex4) is a promising drug for diabetes mellitus with a half-life of 2.4 h in human bodies. Besides, the Ex4 formulations currently employed in the clinic or under development have problems pertaining to stability. In this study, palmitic acid-modified Ex4 (Pal-Ex4) was prepared and purified to extend the half-life of Ex4. In addition, Pal-Ex4-MVLs were further designed and optimized as a long-acting delivery system for intramuscular injection.
METHODS: Pal-Ex4 was encapsulated within multivesicular liposomes (MVLs) via a two-step double emulsification process. The formulated products were then assessed for their vesicle size, encapsulation efficiency, and in vitro and in vivo.
RESULTS: Pal-Ex4-MVLs with a notable encapsulation efficiency of 99.18% were successfully prepared. Pal-Ex4-MVLs, administered via a single intramuscular injection in Sprague-Dawley rats, sustained stable plasma concentrations for 168 h, presenting extended half-life (77.28 ± 12.919 h) and enhanced relative bioavailability (664.18%). MVLs protected Ex4 through providing stable retention and slow release. This approach considerably improved the in-situ stability of the drug for intramuscular administration.
CONCLUSIONS: The combination of palmitic acid modification process with MVLs provides dual protection for Ex4 and can be a promising strategy for other hydrophilic protein/polypeptide-loaded sustained-release delivery systems with high drug bioactivity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Expert opinion on drug delivery - 21(2024), 1 vom: 01. Jan., Seite 169-185 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tian, Huixian [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.02.2024 Date Revised 02.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/17425247.2024.2305110 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367145944 |
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| 245 | 1 | 0 | |a Intramuscular injection of palmitic acid-conjugated Exendin-4 loaded multivesicular liposomes for long-acting and improving in-situ stability |
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| 500 | |a Date Revised 02.02.2024 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Exendin-4 (Ex4) is a promising drug for diabetes mellitus with a half-life of 2.4 h in human bodies. Besides, the Ex4 formulations currently employed in the clinic or under development have problems pertaining to stability. In this study, palmitic acid-modified Ex4 (Pal-Ex4) was prepared and purified to extend the half-life of Ex4. In addition, Pal-Ex4-MVLs were further designed and optimized as a long-acting delivery system for intramuscular injection | ||
| 520 | |a METHODS: Pal-Ex4 was encapsulated within multivesicular liposomes (MVLs) via a two-step double emulsification process. The formulated products were then assessed for their vesicle size, encapsulation efficiency, and in vitro and in vivo | ||
| 520 | |a RESULTS: Pal-Ex4-MVLs with a notable encapsulation efficiency of 99.18% were successfully prepared. Pal-Ex4-MVLs, administered via a single intramuscular injection in Sprague-Dawley rats, sustained stable plasma concentrations for 168 h, presenting extended half-life (77.28 ± 12.919 h) and enhanced relative bioavailability (664.18%). MVLs protected Ex4 through providing stable retention and slow release. This approach considerably improved the in-situ stability of the drug for intramuscular administration | ||
| 520 | |a CONCLUSIONS: The combination of palmitic acid modification process with MVLs provides dual protection for Ex4 and can be a promising strategy for other hydrophilic protein/polypeptide-loaded sustained-release delivery systems with high drug bioactivity | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a in-situ stability | |
| 650 | 4 | |a intramuscular injection | |
| 650 | 4 | |a long-acting treatment | |
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| 650 | 4 | |a palmitic acid | |
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| 700 | 1 | |a Chang, Minsi |e verfasserin |4 aut | |
| 700 | 1 | |a Lyu, Yanlin |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Nini |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a He, Haibing |e verfasserin |4 aut | |
| 700 | 1 | |a Gou, Jingxin |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Xing |e verfasserin |4 aut | |
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