Fucoidan nanogels and methods of their use and manufacture
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.
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.