EFFICIENT LIPOSOMAL ENCAPSULATION UNDER MILD CONDITIONS

摘要

The present invention concerns a method of encapsulating at least one biologically active substance in liposomes under mild conditions. The method for preparing liposomes containing at least one biologically active substance encapsulated therein under mild conditions comprises the following steps: (A) (a) (i) providing liposomes, wherein the liposomes are prepared by a method other than the instant method; and (ii) mixing the liposomes of step (A)(a)(i) with the at least one biologically active substance; (b) (i) providing liposomes in aqueous medium U, wherein the liposomes are prepared by a method other than the instant method; and (ii) mixing the liposomes of step (A)(b)(i) with the at least one biologically active substance; (c) (i) providing liposomes, wherein the liposomes are prepared by a method other than the instant method; and (ii) mixing the liposomes of step (A)(c)(i) with aqueous medium U and the at least one biologically active substance; (d) (i) providing liposomes in aqueous medium U, wherein the liposomes are prepared by a method other than the instant method; and (ii) mixing the liposomes of step (A)(d)(i) with aqueous medium U and the at least one biologically active substance; or (e) forming liposomes in the presence of the at least one biologically active substance by a method other than the instant method; (B) (a) mixing the product of step (A)(b), (A)(c) or (A)(d) with a water-miscible organic solvent to form a gel or a liquid containing gel particles; or (b) mixing the product of step (A)(a) or (A)(e) with aqueous medium U and a water-miscible organic solvent to form a gel or a liquid containing gel particles; and thereafter (C) (a) mixing the gel or liquid containing gel particles with aqueous medium V to directly form the liposomes containing the at least one biologically active substance encapsulated therein, or (b) (i) mixing the gel or liquid containing gel particles with aqueous medium V to form a waxy substance; and (ii) mixing the waxy substance with aqueous medium W to directly form the liposomes containing the at least one biologically active substance encapsulated therein, wherein aqueous media U, V and W are the same or different.