Fucoidan nanogels and methods of their use and manufacture

Patent metadata

Field	Value
Publication number	US-9737614-B2
Application number	US-201615069311-A
Country	US
Kind code	B2
Filing date	Mar 14, 2016
Priority date	Apr 17, 2014
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

Abstract

Described herein are polymeric drug-carrying nanogels that are capable of targeting to P-selectin for the treatment of cancer and other diseases and conditions associated with P-selectin. Furthermore, in certain embodiments, the nanogels presented here offer a drug release mechanism based on acidic pH in the microenvironment of a tumor, thereby providing improved treatment targeting capability and allowing use of lower drug doses, thereby reducing toxicity.

First claim

What is claimed is:

1. A polymeric nanoparticle with affinity to P-selectin, the nanoparticle comprising
a non-covalent assembly of:
(i) a sulfated polymer species comprising free hydroxyl moieties and free sulfate moieties capable of targeting P-selectin; and
(ii) a hydrophobic drug,

wherein the nanoparticle has an average particle diameter of between about 20 and about 200 nm, and wherein the non-covalent assembly is a self-assembly of the sulfated polymer species around the hydrophobic drug.

2. The nanoparticle of claim 1 , wherein the sulfated polymer species comprises one or more members selected from the group consisting of a sulfated polysaccharide, protein, and a fucoidan.

3. The nanoparticle of claim 1 , wherein the sulfated polymer species comprises a fucoidan.

4. The nanoparticle of claim 1 , wherein the hydrophobic drug comprises a member selected from the group consisting of paclitaxel, MEK162, docetaxel, Camptothecin, sorafenib, ispinesib, LY294002, Selumetinib, PD184352, 5-fluorouracil, Cyclophosphamide, Atorvastatin, Lovastatin, etoposide, dexamethasone, gemcitabine, Rapamycin (Sirolimus), and methotrexate.

5. The nanoparticle of claim 1 , wherein the nanoparticle has an average particle diameter of from about 100 nm to about 200 nm.

6. The nanoparticle of claim 1 , wherein the nanoparticle further comprises a fluorophore.

7. The nanoparticle of claim 6 , wherein the fluorophore is a near infra-red dye.

8. The nanoparticle of claim 7 , wherein the infra-red dye is IR783.

9. A method for manufacturing the nanoparticle of claim 1 , the method comprising:
contacting the hydrophobic drug to the sulfated polymer species to form a mixture; and
agitating the mixture to form nanoparticles.

10. The method of claim 9 , wherein agitating the mixture comprises sonicating the mixture.

11. The method of claim 9 , wherein the hydrophobic drug and the sulfated polymer species are precipitated together.

12. The method of claim 9 , wherein the hydrophobic drug and the sulfated polymer species are precipitated together via nano-precipitation.

13. The nanoparticle of claim 1 , wherein the nanoparticle is negatively charged.

Assignees

• Memorial Sloan Kettering Cancer Center

Inventors

• Heller Daniel A
• Shamay Yosef

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6939

  the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin · CPC title

• A61K9/5146

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides · 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

• A61K47/6935

  the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol · CPC title