Micellic assemblies

Patent metadata

Field	Value
Publication number	US-10420790-B2
Application number	US-201715499683-A
Country	US
Kind code	B2
Filing date	Apr 27, 2017
Priority date	May 13, 2008
Publication date	Sep 24, 2019
Grant date	Sep 24, 2019

Abstract

Provided herein are micellic assemblies comprising a plurality of copolymers. In certain instauces, micellic assemblies provided herein are pH sensitive particles.

First claim

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A micellic assembly comprising a plurality of membrane destabilizing block copolymers, the micellic assembly comprising a core and a shell,
wherein the core comprises a plurality of core blocks of the membrane destabilizing block copolymers,
wherein the shell comprises a plurality of shell blocks of the membrane destabilizing block copolymers,
wherein the core block is a copolymer block that is a pH dependent membrane destabilizing hydrophobe comprising
(i) a plurality of a first chargeable monomeric unit that is a (C 2 -C 8 )alkylacrylic acid,
(ii) a plurality of a second chargeable monomeric unit selected from the group consisting of N,N-di(C 1 -C 6 )alkyl-amino(C 1 -C 6 )alkyl-ethacrylate, N,N-di(C 1 -C 6 )alkyl-amino(C 1 -C 6 )alkyl-methacrylate, and N,N-di(C 1 -C 6 )alkyl-amino(C 1 -C 6 )alkyl-acrylate, and
(iii) a plurality of a hydrophobic monomeric unit selected from the group consisting of (C 2 -C 8 )alkyl-ethacrylate, (C 2 -C 8 )alkyl-methacrylate, and (C 2 -C 8 )alkyl-acrylate, and

wherein the shell block is hydrophilic at about neutral pH.

2. The micellic assembly of claim 1 , wherein the first chargeable monomeric unit has a pK a of about 6.7.

3. The micellic assembly of claim 1 , wherein the second chargeable monomeric unit has a pK a of about 6.5 to about 9.

4. The micellic assembly of claim 1 , wherein the first chargeable monomeric unit is propyl acrylic acid (PAA), the second chargeable monomeric unit is dimethylaminoethylmethacrylate (DMAEMA), and the hydrophobic monomeric unit is butyl methacrylate (BMA).

5. The micellic assembly of claim 1 , wherein the shell block is non-charged.

6. The micellic assembly of claim 1 , wherein the shell block comprises a polyethylene glycol (PEG) group.

7. The micellic assembly of claim 3 , wherein the shell block comprises a plurality of shell monomeric units and wherein one or more of the plurality of shell monomeric units are substituted with the PEG group.

8. The micellic assembly of claim 1 , wherein the shell block is formed by co-polymerization of a monomer comprising a polyethylene glycol (PEG) group of 2-20 ethylene oxide units.

9. The micellic assembly of claim 1 , wherein the ratio of the number average molecular weight of the core block to the number average weight of the shell block is from 1:1 to 5:1.

10. The micellic assembly of claim 1 , wherein the membrane destabilizing block copolymers are diblock copolymers.

11. The micellic assembly of claim 1 , wherein the membrane destabilizing block copolymers have been synthesized using Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization.

12. The micellic assembly of claim 1 , wherein the micellic assembly comprises a targeting moiety.

13. The micellic assembly of claim 12 , wherein the targeting moiety is an antibody, a peptide, or a small molecule, wherein the small molecule is a vitamin or a sugar.

14. The micellic assembly of claim 12 , wherein the targeting moiety is a small molecule, wherein the small molecule is a vitamin or a sugar.

15. The micellic assembly of claim 14 , wherein the small molecule is folate or galactose.

16. The micellic assembly of claim 12 , wherein the targeting moiety binds to the asialoglycoprotein receptor.

17. The micellic assembly of claim 12 , wherein the targeting moiety is attached to the shell block of the membrane destabilizing block copolymers.

18. The micellic assembly of claim 1 , wherein the membrane destabilizing block copolymers have a polydispersity index (PDI) of less than 1.6.

19. The micellic assembly of claim 1 , wherein the micellic assembly has an average hydrodynamic diameter of 50 nm or less.

Assignees

• Univ Washington
• Genevant Sciences Gmbh

Inventors

• Stayton Patrick S
• Hoffman Allan S
• Convertine Anthony
• Duvall Craig L
• Benoit Danielle
• Overell Robert
• Johnson Paul H
• Gall Anna S
• Prieve Mary G
• Paschal Amber E E
• Diab Charbel
• De Priyadarsi

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title