Liposome encapsulated amphiphilic drug compositions
AssigneeVrije Universiteit Brussel
InventorsFrederic Camu, Mokarram Alafandy, Robert Brasseur, Franz Legros, Oliver Bouffioux
Life of this patent
Estimating the term…
Abstract
A process for the entrapment of amphiphilic compounds as uncharged or ionic with different mole ratios of phospholipid to the amphiphilic compound. Preparations of ionic species of amphiphilic compounds in the absence of crystals can be prepared, while preparations of uncharged amphiphilic compounds can be prepared with the compound exclusively entrapped inside the liposomes, or partly entrapped inside the liposomes with extraliposomal crystals.
Claims27
A process for preparing multilamellar liposomes and incorporating within the phospholipid bilayers thereof ionic species of amphiphilic compounds comprising a hydrophilic and a hydrophobic portion, which method comprises the steps of:
- i) selecting an amphiphilic compound the ionic species of which will at least partly insert into the liposomal phospholipid bilayers by numeric molecular modelling or conformational analysis;
- ii) extracting the hydrophilic ionic species of the said amphiphilic compound from an aqueous medium by means of an organic solvent in which the phospholipid is dissolved;
- iii) preparing a lipid film comprising the phospholipid and the amphiphilic compound by the evaporation to dryness of this solution;
- and
- iv) preparing a suspension of multilamellar liposomes by hydration of the lipid film at an acidic pH in the range of from 4 and to 6.5, whereby the ionic species of the amphiphilic compound is at least partly inserted into the phospholipid layer beneath the fatty acid C.sub.2 -C.sub.3 hydrophilic interface.
A process for preparing multilamellar liposomes and incorporating within the phospholipid bilayers thereof uncharged amphiphilic compounds comprising a hydrophilic and a hydrophobic portion, which method comprises the steps of
- a) wherein the molar ratio of the phospholipid/compound at which the compound is exclusively entrapped inside the liposomes without crystals of the compound, or is partly entrapped in the liposomes with extraliposomal crystals, but no intraliposomal crystals, is predetermined by progressively increasing the phospholipid/compound mole ratio, hydrating the films as multilamellar vesicles suspensions and determining the presence of or the absence of extraliposomal crystals or intraliposomal crystals by light and/or electron microscopy;
- b) dissolving the apolar hydrophobic species of the amphiphilic compound in the phospholipid bilayers using the predetermined phospholipid/compound mole ratios to obtain preparations of liposomes with the compound exclusively entrapped inside the liposomes without crystals of the compound, or partly entrapped inside the liposomes with extraliposomal crystals;
- c) preparing a lipid film comprising the phospholipid and the amphiphilic compound by the evaporation to dryness of this solution;
- and
- d) preparing a suspension of multilamellar liposomes by hydration of the lipid film at a pH at which the amphiphilic compound remains in the uncharged form, whereby that the amphiphilic compound is at least partly inserted into the phospholipid layer beneath the phospholipid fatty acid C.sub.2 -C.sub.3 hydrophobic/hydrophilic interface.
Dependencies are inferred from the claim text.