A lipid based delivery system for the peroral administration of an orally inactive peptide drug (Myrcludex B)

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The oral delivery of of peptides/proteins gernerally fails due to instability and low absorption in the gastrointestinal tract (GI-tract) . In this project we will study a liposomal carrier system containing tetraether lipids (TELs) from Archaeae. Preliminary studies show an extremely increased stability of such liposomes in the GI-tract compared to conventional liposomes. By dual asymmetric centrifugation peptides can be incorparated into these liposomes to a very high extent. First studies in rats show a significantly increased bioavailability of incorporated peptides in rats compared to dissolved drugs (26-fold for octreotide (MW 1,17 kDa), ca 360-fold for human growth hormone MW ca 23,5 kDa). This system should now enable the oral administration of the hepatitis B virus (HBV) therapeuticum Myrcludex B. This drug, being in phase 2- clinical tests, is derived from an enevelope protein of the virus. It exhibits an extreme hepatotropism and inhibits hepatitis B and D infection at pricomolar concentrations. However its bioavailability after oral administration is zero. This peptide will be incroporated into TEL-liposomes. Thereby, loading capacity, liposomes size, stability under various conditions, release properties and development of a formaulation, which is applicable to humans will be studied. Then, a bioavailability study in rats as well as a proof-of-concept study in a rodent hepatitis model (HBV-positive mice) will be performed in collaboration with Prof. Urban, Heidelberg, in order to demonstrate the efficiency of this liposomal peptide system after oral administration.