Prodrug compositions, prodrug nanoparticles, and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11141379-B2
Application number	US-201816234044-A
Country	US
Kind code	B2
Filing date	Dec 27, 2018
Priority date	Apr 15, 2010
Publication date	Oct 12, 2021
Grant date	Oct 12, 2021

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 to a target cell, the composition comprising a non-liposomal particle and at least one prodrug, wherein:
(a) the particle has an outer surface that is a membrane comprised of the at least one prodrug, about 100 mol % to about 60 mol % phospholipid, and a homing ligand, and an inner core comprising a surfactant;
(b) the particle has a hydrodynamic diameter that is about 10 to about 20 nm, as measured by dynamic light scattering;
(c) the prodrug comprises a compound of less than about 3000 da linked to an acyl moiety of a phosphoglyceride, wherein the compound may be released from the phosphoglyceride backbone via enzyme cleavage; and
(d) the particle can leave blood vessels while circulating through the body.

2. The composition of claim 1 , wherein the surfactant is selected from the group consisting of polysorbate 80, sorbitan monooleate, sorbitan sesquioleate, and sorbitan monolaurate.

3. The composition of claim 1 , wherein the outer surface of the particle is comprised of not more than 3 mol % of a prodrug.

4. The composition of claim 1 , wherein the outer surface of the particle is comprised of about 0.1 mol % of a prodrug to about 9% of a prodrug.

5. The composition of claim 1 , wherein the non-liposomal particle is a micelle.

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

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

8. 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.

9. The composition of claim 1 , wherein the homing ligand is selected from the group consisting of integrins αvβ3, α5β1, ICAM-1, VCAM-1 and VLA-4.

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

11. The composition of claim 10 , wherein the acyl moiety of the prodrug is at least 4 carbon atoms in length from the glycerol backbone sn-2 ester bond.

12. The composition of claim 1 , wherein the compound is docetaxel or paclitaxel.

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

14. The composition of claim 1 , wherein the compound is camptothecin.

15. The composition of claim 14 , wherein the prodrug is

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

17. 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.

18. The method of claim 17 , wherein the composition is administered intravenously.

Assignees

• Univ Washington

Inventors

• Lanza Gregory M
• Pan Dipanjan

Classifications

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K31/336

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

• A61K41/0071

  PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines · CPC title

• A61K47/555

  pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells · CPC title

• A61K47/6907

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