A liposomal formulation for the oral application of the investigational hepatitis B drug Myrcludex B
The aim of this study was the development of a liposomal formulation containing specific tetraether lipids for the oral administration of the investigational hepatitis B peptide drug Myrcludex B. For this purpose, tetraether lipids were extracted from the extremophilic archaeon Sulfolobus acidocalda...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2 April 2016
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| In: |
European journal of pharmaceutics and biopharmaceutics
Year: 2016, Volume: 103, Pages: 159-166 |
| ISSN: | 1873-3441 |
| DOI: | 10.1016/j.ejpb.2016.03.031 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.ejpb.2016.03.031 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0939641116301217 
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| Author Notes: | P. Uhl, F. Helm, G. Hofhaus, S. Brings, C. Kaufman, Karin Leotta, S. Urban, U. Haberkorn, W. Mier, G. Fricker |
| Summary: | The aim of this study was the development of a liposomal formulation containing specific tetraether lipids for the oral administration of the investigational hepatitis B peptide drug Myrcludex B. For this purpose, tetraether lipids were extracted from the extremophilic archaeon Sulfolobus acidocaldarius and purified in order to obtain the desired glycerylcaldityltetraether lipids (GCTE). Myrcludex B was synthesized by solid-phase synthesis and incorporated into liposomes containing 5mol% of GCTE. These liposomes showed a size, polydispersity index and zeta potential comparable to the standard liposomes. Cryo-EM micrographs of both liposomal formulations displayed low lamellarity, the prerequisite for high drug loading capacity. Long term storage of the GCTE-liposomes was achieved by freeze-drying using 100-500mM sucrose or trehalose as lyoprotectors. The lyophilized product showed high stability with a recovery rate of 82.7±1.6% of intact Myrcludex B observed after storage for 3months at −20°C as compared to a recovery rate of 83.3±1.3% directly after the freeze-drying process. In vivo, the GCTE-liposomal formulation led to substantial enhancement of the liver uptake of iodine-131-labeled Myrcludex B in Wistar rats. 3h after oral application, approximately 7% of the initial dose (corresponding to a 3.5-fold increase compared to the free peptide) could be detected in the liver. In summary, the GCTE-liposomes enabled efficient oral administration of Myrcludex B and provided long term storage by freeze-drying. |
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| Item Description: | Gesehen am 14.08.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1873-3441 |
| DOI: | 10.1016/j.ejpb.2016.03.031 |