Lipid-based mixed micelles for oral delivery of vitamin K

Abstract

Konakion® MM (composed of egg phosphatidylcholine, glycocholic acid and vitamin K) fails to prevent vitamin K deficiency bleeding (VKDB) in cholestatic infants due to impaired intestinal absorption of vitamin K. Glycocholic acid is one of the components of the Konakion® MM formulation and has a carboxylic acid group with a pKa of 3.8, which ensures, due to charge repulsion, a good colloidal stability of the formulation at pH>4. However, the formulation is unstable and aggregates at low gastric pH because of protonation of this carboxylate group, causing coalescence of the micelles. In this thesis, mixed micelle formulations of vitamin K were developed to overcome the disadvantage of the clinically used Konakion® MM formulation (unstable at low pH) and thus potentially provide better protection against VKDB, especially for patients suffering from cholestasis. Two different strategies were exploited, namely the introduction of poly(ethylene glycol) as a steric barrier (by partially replacing egg phosphatidylcholine in Konakion® MM by DSPE-PEG 2000, a non-ionic surfactant),and the partial replacement of glycocholic acid of Konakion® MM by non-ionic surfactants-saponins.