Methods of lyophilizing lipid nanoparticles
AssigneeTakeda Pharmaceutical Company Limited
InventorsKanika Suri, Amit Singh, Amiji M. Mansoor
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Abstract
This disclosure features novel lipid nanoparticle formulations and uses thereof. The lipid nanoparticle (“LNP”) includes an encapsulated therapeutic agent and an aqueous solution comprising a salt and an anionic polymer, wherein the salt and the anionic polymer are dissolved in the aqueous solution, thereby forming polymer coated lipid nanoparticle (“PCLNP”). Lipid nanoparticles of this disclosure are useful in the process of lyophilization or freeze drying and decrease nanoparticle aggregation and maintain efficacy once reconstituted.
Claims72
A composition comprising at least one lipid nanoparticle encapsulating a therapeutic agent and an aqueous solution comprising a salt and an anionic polymer, wherein the salt and the anionic polymer are dissolved in the aqueous solution.
The composition from any one of the previous claims, wherein the aqueous solution comprising a salt is selected from the group consisting of HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), PBS (phosphate buffered saline), TRIS (tris(hydroxymethyl)aminomethane), MES (2-(N-morpholino)ethanesulfonic acid), and citrate buffer.
The composition of any one of the previous claims, wherein the composition further comprises a sugar.
The composition of any one of the previous claims, wherein the nucleic acid molecule is a short interfering RNA, the anionic polymer is a methacrylic acid polymer, and the lipid nanoparticle comprises at least one lipid selected from the group consisting of a cationic lipid, a polar lipid, a zwitterionic lipid, or a combination thereof.
The composition of any one of the previous claims, wherein the wherein the nucleic acid molecule is a short interfering RNA, the anionic polymer is a methacrylic acid polymer, and the lipid nanoparticle comprises at least one cationic lipid.
A method of producing a pharmaceutical composition, comprising
- a) producing lipid nanoparticles from at least one lipid and at least one nucleic acid molecule;
- and
- b) mixing an aqueous solution comprising a salt and an anionic polymer with the lipid nanoparticles produced in step a) and a pharmaceutically acceptable carrier.
A method of stabilizing a lipid nanoparticle for lyophilization, the method comprising:
- a) producing lipid nanoparticles from the at least one lipid and the at least one nucleic acid molecule;
- b) mixing an aqueous solution comprising a salt and an anionic polymer with the lipid nanoparticles produced in step a);
- and
- c) lyophilizing the resulting mixture,
- thereby stabilizing the lyophilized lipid nanoparticle.
A method of manufacturing a stable pharmaceutical composition, the method comprising:
- a) dissolving an anionic polymer in an aqueous solution comprising a salt;
- and
- b) mixing the dissolved anionic polymer with a lipid nanoparticle comprising at least one nucleic acid.
The method of claim of 53, wherein the amount of sugar is about 5%.
Dependencies are inferred from the claim text.