Materials and methods for targeting therapeutic compositions to gut-associated lymphoid tissue (GALT)

Patent metadata

Field	Value
Publication number	US-9872859-B2
Application number	US-201715437878-A
Country	US
Kind code	B2
Filing date	Feb 21, 2017
Priority date	Feb 20, 2016
Publication date	Jan 23, 2018
Grant date	Jan 23, 2018

Abstract

The present invention provides novel, long-acting nanoformulated drugs and targeted drug delivery methods, and uses thereof. In one embodiment, the nanoformulated drug is a retroviral drug. In one embodiment, the nanoformulated composition comprises a nanocarrier with one or more incorporated drugs. In an exemplary embodiment, the drug is efavirenz (EFV). In a further embodiment, the nanocarrier is associated with an agent for targeting microfold cells (M-cells). In a specific embodiment, the targeting agent binds to an M-cell marker known as glycoprotein 2 (GP2). Via this mechanism, the nanodrug is targeted toward GALT.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising a nanodrug that comprises an active agent, a poloxamer, and an antibody to glycoprotein-2 (GP2) or antibody fragment to GP2 that targets microfold cells (M-cells) and facilitates the uptake of the nanodrug by M-cells.

2. The pharmaceutical composition, according to claim 1 , in which the poloxamer is F127COOH.

3. The pharmaceutical composition, according to claim 2 , having F127COOH conjugated to GP2.

4. The pharmaceutical composition, according to claim 1 , comprising a retroviral agent as the active agent.

5. The pharmaceutical composition, according to claim 4 , wherein the retroviral agent is efavirenz.

6. The pharmaceutical composition, according to claim 1 , comprising a latency activating drug.

7. The pharmaceutical composition, according to claim 1 , wherein the nanodrug is encapsulated in an enteric coating that resists degradation at pHs below 5.0 and releases the nanodrug at a pH above 5.0.

8. A method of delivering an active agent to gut-associated lymphoid tissue (GALT) comprising administering, to a subject, a pharmaceutical composition comprising a nanodrug that comprises an active agent, a poloxamer, and an antibody to GP2 or antibody fragment to GP2 that targets M-cells and facilitates the uptake of the nanodrug by M-cells.

9. The method, according to claim 8 , used to deliver a retroviral drug directly to GALT and beyond.

10. The method, according to claim 8 , wherein a sustained release of the active agent occurs.

11. The method, according to claim 8 , used to treat HIV in the subject.

12. The method, according to claim 8 , in which the poloxamer is F127COOH.

13. The method, according to claim 8 , wherein the subject is a human or mouse and the composition is administered intravenously, intraperitoneally, or subcutaneously.

14. The method, according to claim 9 , wherein the retroviral drug is efavirenz.

15. The method, according to claim 8 , wherein the pharmaceutical composition comprises a latency activating drug.

16. The method, according to claim 8 , wherein the nanodrug is encapsulated in an enteric coating that resists degradation at pHs below 5.0 and releases the nanodrug at a pH above 5.0.

17. A pharmaceutical composition comprising a nanodrug comprising efavirenz and F127COOH conjugated to anti-GP2 antibody that facilitates the uptake of the nanodrug by M-cells, and wherein the nanodrug is coated with an enteric coating that degrades only at a pH above 5.0.

18. A method of delivering an active agent to gut-associated lymphoid tissue (GALT) comprising administering, to a subject, a pharmaceutical composition comprising a nanodrug comprising a F127COOH micelle conjugated to anti-GP2 antibody that facilitates the uptake of the F127COOH micelle by M-cells, and further comprising efavirenz encapsulated in the F127COOH micelle, characterized in that the nanodrug is coated with an enteric coating that degrades only at a pH above 5.0.

19. The method, according to claim 18 , in which the F127COOH micelle has a size of 120-140 nm.

Assignees

• Roy Upal
• Ding Hong
• Nair Madhavan
• The Florida International Univ Board Of Trustees

Inventors

• Roy Upal
• Ding Hong
• Nair Madhavan

Classifications

• A61K47/48561

  Human Necessities · mapped topic

• A61K47/48215

  Human Necessities · mapped topic

• A61K47/488

  Human Necessities · mapped topic

• A61K31/536 Primary

  ortho- or peri-condensed with carbocyclic ring systems · CPC title

• A61K47/6907

  the form being a microemulsion, nanoemulsion or micelle · CPC title