Amphiphile-polymer particles

Patent metadata

Field	Value
Publication number	US-10583091-B2
Application number	US-201515520796-A
Country	US
Kind code	B2
Filing date	Oct 23, 2015
Priority date	Oct 23, 2014
Publication date	Mar 10, 2020
Grant date	Mar 10, 2020

Abstract

This invention relates to amphiphile-polymer particles comprising obtaining a first solution comprising a water-insoluble polymer, a payload and a first amphiphile in a water-miscible solvent; mixing the first solution with an aqueous second solution to form an aqueous composition comprising a particle comprising a water-insoluble polymeric core comprising the water-insoluble polymer; the payload; and the first amphiphile.

First claim

What is claimed is:

1. A particle comprising:
a water-insoluble polymeric core; and
a nucleic acid and a first amphiphile comprising an amino dendrimer comprising a lipophilic moiety selected from the group consisting of G0-C14 dendrimer, polypropyleneimine tetramine dendrimer generation 1, and ethylenediamine branched polyethyleneimine within the core.

2. The particle of claim 1 , further comprising a shell comprising a second amphiphile surrounding the water-insoluble polymeric core.

3. The particle of claim 1 , wherein the water-insoluble polymeric core comprises one or more polymers selected from a polylactic acid, a polyglycolic acid, and a copolymer of lactic acid and glycolic acid.

4. The particle of claim 2 , wherein the second amphiphile comprises one or more compounds selected from neutral, cationic and anionic lipids, PEG-phospholipid, and a PEG-ceramide.

5. The particle of claim 4 , wherein the neutral, cationic or anionic lipid is lecithin; the PEG-phospholipid is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000] or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; and the PEG-ceramide is N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)5000]}.

6. A particle prepared by a process comprising:
obtaining a first solution comprising a water-insoluble polymer, a nucleic acid and a first amphiphile comprising an amino dendrimer comprising a lipophilic moiety selected from the group consisting of G0-C14 dendrimer, polypropyleneimine tetramine dendrimer generation 1, and ethylenediamine branched polyethyleneimine in a water-miscible solvent; and
mixing the first solution with an aqueous second solution to form an aqueous composition comprising the particle.

7. The particle of claim 6 , wherein the process further comprises mixing the aqueous composition with a solution comprising a second amphiphile to form a shell surrounding the core.

8. A pharmaceutical composition comprising the particle of claim 1 , and a pharmaceutically acceptable carrier.

9. A method of preparing a particle according to claim 1 , the method comprising:
obtaining a first solution comprising a water-insoluble polymer, a nucleic acid and a first amphiphile comprising an amino dendrimer comprising a lipophilic moiety selected from the group consisting of G0-C14 dendrimer, polypropyleneimine tetramine dendrimer generation 1, and ethylenediamine branched polyethyleneimine in a water-miscible solvent; and
mixing the first solution with an aqueous second solution to form an aqueous composition comprising the particle.

10. The method of claim 9 , further comprising mixing the aqueous composition with a solution comprising a second amphiphile to form a shell surrounding the core.

11. A method of administering a nucleic acid to a subject, the method comprising administering to the subject in need thereof a pharmaceutical composition according to claim 8 .

12. The particle of claim 1 , further comprising a small-molecule drug within the core.

13. The particle of claim 6 , wherein the first solution further comprises a small-molecule drug.

14. The method of claim 9 , wherein the first solution further comprises a small-molecule drug.

15. The particle of claim 1 or 6 , wherein the nucleic acid comprises siRNA.

16. The particle of claim 1 or 6 , wherein the nucleic acid comprises mRNA.

17. The particle of claim 1 or 6 , wherein the nucleic acid comprises microRNA.

18. The method of claim 9 , wherein the nucleic acid comprises siRNA.

19. The method of claim 9 , wherein the nucleic acid comprises mRNA.

20. The method of claim 9 , wherein the nucleic acid comprises microRNA.

Assignees

• Brigham & Womens Hospital Inc
• Harvard College

Inventors

• Shi Jinjun
• Zhu Xi
• Farokhzad Omid C
• Xu Xiaoding
• Liu Yanlan
• Thiriot Aude
• Von Andrian Ulrich

Classifications

• A61K38/43

  Enzymes; Proenzymes; Derivatives thereof · CPC title

• A61K9/5153 Primary

  Polyesters, e.g. poly(lactide-co-glycolide) · CPC title

• A61K9/5078

  with drug-free core · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K9/5031

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide) · CPC title