HEPARIN COATED LIPID NANOSPHERE CONTAINING AMPHOTERICIN B AND PREPARATION METHOD OF THE SAME

摘要

A lipid nanosphere encapsulating amphotericin B is provided to coat the lipid nanosphere surface with heparin by using an anionic phospholipid or introducing a polymer having a polyethyleneglycol(PEG) group thereinto, thereby increasing circulation time in a body and decreasing toxicity of the amphotericin B. A lipid nanosphere encapsulating amphotericin B is characterized in that a PEG is exposed to the surface of the lipid nanosphere including an anionic phospholipid and the surface of the lipid nanosphere is coated with heparin to prolong circulation time in a body. A method for preparing the lipid nanosphere comprises the steps of: (a) after mixing phosphatidylcholine, the anionic phospholipid, sterol and a polymer having a PEG group in a weight ratio of 40-70:5-20:10-40:10-30, dissolving the mixture in an organic solvent; (b) dissolving the amphotericin B in a linear or branched C1-6 alcohol; (c) mixing the solution obtained from the step(a) and the solution obtained from the step(b) in a volumetric ratio of 1:1-1:9; (d) dispersing the mixture solution into an aqueous phase in a volumetric ratio of 2:1-1:10 to form the lipid nanosphere; (e) after distilling the lipid nanosphere solution at a temperature of 20-50 deg.C under reduced pressure to remove the organic solvent therefrom, filtering it to prepare the anionic lipid nanosphere encapsulating the amphotericin B; (f) mixing the lipid nanosphere obtained from the step(e) with heparin to have the lipid forming the lipid nanosphere and the heparin in a weight ratio of 100:0.1-100:10; and (g) removing the heparin or a derivative therefor not-coating the lipid nanosphere from the mixture solution of the step(f). Further, an average molecular weight of the heparin is 500 to 50000.