Lipidated glycosaminoglycan particles for the delivery of nucleic acids

Patent metadata

Field	Value
Publication number	US-9925143-B2
Application number	US-201314395198-A
Country	US
Kind code	B2
Filing date	Mar 14, 2013
Priority date	Apr 18, 2012
Publication date	Mar 27, 2018
Grant date	Mar 27, 2018

Abstract

There are provided compositions comprising lipidated glycosaminoglycan particles, methods for their preparation and uses thereof for the efficient in-vivo and in-vitro delivery of nucleic acids, such as, siRNA molecules.

First claim

What is claimed is:

1. A composition comprising water insoluble lipidated glycosaminoglycan particles comprising
(i) a plurality of lipids forming a particulate lipid composition, wherein the plurality of lipids comprises monocationic lipid N-[1-(2,3-Dioleoyloxy)]-N,N,N-trimethylammonium propane (DOTAP), 1,2-dilauroyl-Lphosphatidyl-ethanolamine (DLPE), and cholesterol, wherein the relative molar amount of DOTAP is greater than the relative molar amount of DLPE and the relative molar amount of cholesterol, and wherein the relative amount of DLPE in the composition is 11% to about 25%, and
(ii) a nucleic acid encapsulated within the particles,
wherein the weight ratio of the nucleic acid to lipids is less than 1:1, and wherein the composition is not a liposome.

2. The composition of claim 1 , wherein the glycosaminoglycan is selected from hyaluronic acid, Chondroitin sulfate, Dermatan sulfate, Keratan sulfate, Heparin, Heparan sulfate, salts, and mixtures thereof.

3. The composition of claim 2 , wherein the hyaluronic acid comprises high molecular weight hyaluronic acid.

4. The composition of claim 1 , wherein the particulate lipid composition have a particle size of over about 200 nm.

5. The composition of claim 1 , wherein the nucleic acid comprises DNA, RNA, modified forms thereof, and combinations thereof.

6. The composition of claim 5 , wherein the RNA is selected from siRNA, miRNA, shRNA, antisense RNA and combinations thereof.

7. The composition of claim 1 , wherein the weight ratio between the plurality of lipids and the nucleic acid is 10:1.

8. The composition of claim 1 further comprising a targeting moiety.

9. The composition of claim 1 , wherein the particles are adapted to deliver the nucleic acid to a target site and wherein the target site is selected from the group consisting of a tumor, a cell, a tissue, an organ, and a microorganism.

10. A composition according to claim 1 in the form of freeze dried particles.

11. A pharmaceutical composition comprising the particles according to claim 1 in a dosage form suitable for administration via a route selected from oral, parenteral and topical.

12. The composition of claim 1 , wherein the relative molar amount of DOTAP is about 30-80% and the relative molar amount of cholesterol is about 10-50%.

13. The composition of claim 1 , wherein the relative molar amount of DOTAP is about 50% and the relative molar amount of cholesterol is about 35%.

14. The composition of claim 3 , wherein the molecular weight of the hyaluronic acid is about 3.1×10 5 to about 1.5×10 6 daltons.

Assignees

• Univ Ramot
• Quiet Therapeutics Ltd

Inventors

• Peer Dan
• Alpert Evgenia

Classifications

• A61K47/6939

  the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• C12N15/88 Primary

  using microencapsulation, e.g. using {amphiphile} liposome vesicle · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• A61K47/6941

  the form being a granulate or an agglomerate · CPC title