Charge triggering of self-organized nanoparticles

Patent metadata

Field	Value
Publication number	US-9161993-B2
Application number	US-201214117881-A
Country	US
Kind code	B2
Filing date	May 16, 2012
Priority date	May 16, 2011
Publication date	Oct 20, 2015
Grant date	Oct 20, 2015

Abstract

The present application discloses a nanoparticle comprising compounds of the formula A-B-C(-D), wherein A designates an anchoring moiety having self-organizing properties in relation to the nanoparticle; B designates a cleavable linker; C designates an anionic moiety having a net charge of at least −2 at pH 6.0; and D, which is optional, designates a polymer moiety which induces long circulating properties of the nanoparticle in mammalian tissue; and wherein the average net charge of the compounds is at least −1 at pH 6.0. The application also discloses the individual compounds of the formula A-B-C(-D) as well as a drug delivery system comprising the self-organized nanoparticle having included in the interior thereof one or more pharmaceutically active agents and/or diagnostically relevant species, and a method of treating a cancerous or inflammatory condition in a mammal, involving the administration of the drug delivery system to the mammal.

First claim

The invention claimed is:

1. A nanoparticle selected from the group consisting of a liposome and a lipoplex comprising a compound of the formula A-B-C(-D), wherein
A designates a hydrophobic lipid anchoring moiety;
B designates a cleavable linker;
C designates an anionic moiety having a net charge of from −3 to −30 at pH 6.0; and
D, which is optional, designates a hydrophilic polymer moiety which induces long circulating properties of the nanoparticle in mammalian tissue;
wherein the overall net charge of the compound of formula A-B-C-(D) is from −2 to −25 at pH 6.0;
and wherein the compound of formula A-B-C(-D) is included in an amount of at least 1% by total weight of the nanoparticle.

2. The nanoparticle according to claim 1 , wherein the linker B is cleavable in mammalian tissue.

3. The nanoparticle according to claim 1 , wherein the linker B is cleavable by external stimuli.

4. The nanoparticle according to claim 1 , wherein the linker B is a peptide which is cleavable by a matrix metalloprotease.

5. The nanoparticle according to claim 1 , wherein D is present and is a poly(ethylene glycol).

6. The nanoparticle according to claim 1 , wherein the nanoparticle is a liposome.

7. The nanoparticle according to claim 1 , wherein the nanoparticle is a liposome and wherein the liposome further comprises one or more solid particles in the interior of said liposome.

8. The nanoparticle according to claim 1 , wherein the nanoparticle is a lipoplex.

9. A drug delivery system the nanoparticle of claim 1 further comprising a pharmaceutically active agent and/or a diagnostic agent in the interior of the nanoparticle.

10. A method for the administration of a drug delivery system to a mammal in need thereof comprising the step of administering a drug delivery system of claim 9 to said mammal.

11. A compound of compounds of the formula A-B-C-D, wherein
A designates a hydrophobic lipid anchoring moiety selected from the group consisting of saturated diacyl phospholipids, unsaturated diacyl phospholipids, diacylglycerols and derivatives thereof, sterols, and ceramides;
B designates a cleavable linker selected from the group consisting of peptides which can be activated by proteases, an S-S linkage, and pH sensitive linkers;
C designates an anionic moiety selected from anionic peptides or anionic polymers, having a net charge of from −3 to −30 at pH 6.0; and
D designates a hydrophilic polymer moiety selected from the group consisting of poly(ethylene glycol), dextran, hyaluronan, polyalcohols, and polycarboxylates;
wherein the overall net charge of the compound of formula A-B-C-D is from −2 to −25.

12. A nanoparticle comprising the compound of claim 11 , wherein said nanoparticle is a liposome or a lipoplex, and wherein said compound is included in an amount of at least 1% by total weight of the nanoparticle.

13. The nanoparticle according to claim 12 , wherein the nanoparticle is a liposome.

14. The nanoparticle according to claim 12 , wherein the nanoparticle is a liposome and wherein the liposome further comprises one or more solid particles in the interior of said liposome.

15. A drug delivery system comprising the nanoparticle of claim 12 further comprising a pharmaceutically active agent and/or diagnostically relevant species.

16. A method for the administration of a drug delivery system to a mammal in need thereof comprising the step of administering a drug delivery system of claim 15 to said mammal.

Assignees

• Jølck Rasmus Irming
• Henriksen Jonas Rosager
• Gjetting Torben
• Andresen Thomas Lars
• Univ Danmarks Tekniske

Inventors

• Jølck Rasmus Irming
• Henriksen Jonas Rosager
• Gjetting Torben
• Andresen Thomas Lars

Classifications

• A61K31/7088 Primary

  Compounds having three or more nucleosides or nucleotides · CPC title

• A61K47/48815

  Human Necessities · mapped topic

• A61K47/48338

  Human Necessities · mapped topic

• A61K31/282

  Platinum compounds · CPC title

• Y10S977/801

  Drug · CPC title