Prodrug compositions, prodrug nanoparticles, and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11872313-B2
Application number	US-202017090574-A
Country	US
Kind code	B2
Filing date	Nov 5, 2020
Priority date	Apr 15, 2010
Publication date	Jan 16, 2024
Grant date	Jan 16, 2024

Abstract

The present invention encompasses prodrug compositions, nanoparticles comprising one or more prodrugs, and methods of use thereof.

First claim

What is claimed is:

1. A composition for in vivo delivery of a compound into a target cell, the composition comprising a non-liposomal particle having
an outer surface that is a membrane comprising at least one prodrug, about 100 mol % to about 60 mol % phospholipid, and a homing ligand, wherein the prodrug comprises a compound of less than about 3000 da linked to an acyl moiety of a phosphoglyceride, and the compound may be released from the phosphoglyceride backbone via enzyme cleavage; and
an inner core;

wherein, in vivo, the particle substantially retains the prodrug within the membrane of the particle until the particle fuses with the target cell's membrane and transfers the prodrug from the particle to the target cell membrane, and wherein particle can leave blood vessels while circulating through the body; and
wherein the particle is sized less than 20 nm.

2. The composition of claim 1 , wherein the inner core comprises perfluorocarbon.

3. The composition of claim 1 , wherein the outer surface of the particle is comprised of about 0.1 mol % to about 15 mol % of the prodrug.

4. The composition of claim 1 , wherein the outer surface of the particle is comprised of about 2 mol % to about 10 mol % of the prodrug.

5. The composition of claim 1 , wherein less than about 10% of the outer surface is cross-linked.

6. The composition of claim 1 , wherein the outer surface is not pegylated except for the homing ligand.

7. The composition of claim 1 , wherein the homing ligand is selected from the group consisting of antibodies, antibody fragments, peptides, asialoglycoproteins, polysaccharides, nucleic acids, small molecules, and peptidomimetics.

8. The composition of claim 1 , wherein the compound is linked to the sn-2 acyl moiety of the phosphoglyceride.

9. The composition of claim 8 , wherein the acyl moiety of the prodrug is at least 4 carbon atoms in length from the glycerol backbone sn-2 ester bond.

10. The composition of claim 1 , wherein the compound of less than about 3000 da is selected from the group consisting of a peptide, a peptide mimic or analogue, an organometallic complex, an organic molecule, and a nucleic acid or analogue thereof.

11. The composition of claim 1 , wherein the prodrug is a compound selected from the group consisting of compound

12. The composition of claim 1 , wherein the compound of less than about 3000 da is selected from doxorubicin, docetaxel, methylprednisolone, fumagillin or an analogue thereof, camptothecin or an analogue thereof, a myc inhibitor, and a PDT drug.

13. The composition of claim 1 , wherein the prodrug comprises a phosphoglyceride selected from the group consisting of phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol, and phosphatidyl serine.

14. A method for in vivo delivery of a compound to a target cell, the method comprising administering a composition of claim 1 to a subject.

15. The method of claim 14 , wherein the composition is administered intravenously.

16. The method of claim 14 , wherein the composition is administered parenterally, intraperitoneally, intravascularly, or intrapulmonarily.

Assignees

• Washington University St Louis

Inventors

• Lanza Gregory M
• Pan Dipanjan

Classifications

• A61K9/145 Primary

  with organic compounds · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/1075

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• A61K31/336

  having three-membered rings, e.g. oxirane, fumagillin · CPC title