Oral Application of the Hepatitis B Peptide Drug Myrcludex B

3/22/2022 16:05 - 16:35

Aim of this study was the development of a liposomal formulation containing specific tetraether lipids for the oral administration of the hepatitis B peptide drug Myrcludex B. Tetraether lipids were extracted from extremophilic 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 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% of intact Myrcludex B observed after storage for 3months at -20°C as compared to a recovery rate of 83% directly after the freeze-drying process. In vivo, the GCTE-liposomal formulation led to substantial enhancement of the liver uptake of iodine131-labeled Myrcludex B in Wistar rats. 3h after oral application, approximately 7% of the initial dose 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.

Gert Fricker, Director at the Institute of Pharmacy and Molecular Biotechnology in the Faculty of Biosciences, University of Heidelberg