EP2398463A1 — A method for amphiphilic drug loading in liposomes by ion gradient

USPTO Abstract

An active loading of amphophilic drugs, especially anthracycline antibiotics, in liposomes using conventional lipid compositions, is achieved by applying salts of polycarboxylic acids with mono- or divalent cations, preferably selected from sodium, potassium, calcium, magnesium or ammonium salt of ethylenediaminotetraacetic acid (EDTA) or ethyleneglycol-O-O'-bis(2-aminoethyl)-N,N,N',N'-tetraacetic acid (EGTA). The liposomal formulations obtained by the method of active loading of drugs to liposomes by EDTA or EGTA salts gradient are characterized by high loading efficiency, feature microcrystalline deposits of anthracyclines inside liposomes, which renders them stable and not susceptible to leakage. The liposomes are unilamellar and their size is close to 100 nanometers after drug loading.