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Fucoidan nanogels and methods of their use and manufacture

a technology of fucoidan and nanogels, which is applied in the field of nanogels, can solve the problems of increased apoptosis at the tumor site, prolonged inhibition of erk phosphorylation, etc., and achieve the effects of reducing drug dose, improving treatment targeting capability, and reducing toxicity

Inactive Publication Date: 2015-11-19
MEMORIAL SLOAN KETTERING CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes polymeric nanogels that can target P-selectin, a protein associated with cancer and inflammatory diseases. The nanogels have hydroxyls and sulfates that can bind to P-selectin, and they release drugs in tumors or inflammatory tissues that have acidic pH. This targeting mechanism improves the effectiveness of drugs and reduces the amount needed, which reduces toxicity. The nanogels can also be used for cancer treatment by themselves or in combination with other therapies like chemotherapy or radiotherapy. The patent also mentions that P-selectin is a promising target for drug delivery in various cancers and can be reached using a natural polysaccharide. Overall, this technology can potentially improve the treatment of many diseases associated with P-selectin.

Problems solved by technology

Single-dose administration of an encapsulated reversible MEK inhibitor results in prolonged inhibition of ERK phosphorylation and increased apoptosis at the tumor site.

Method used

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  • Fucoidan nanogels and methods of their use and manufacture
  • Fucoidan nanogels and methods of their use and manufacture
  • Fucoidan nanogels and methods of their use and manufacture

Examples

Experimental program
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experimental examples

Preparation of DOX-PEG-DOX (DPD):

[0145]10 mg of Hydrazide-PEG-hydrazide, NH2NH-PEG-NHNH2, MW 3400 (from NANOCS) and 10 mg Doxorubicin were dissolved in 3 ml methanol containing 100 μL of glacial acetic acid. The mixture was stirred in the dark for 24 h and then slowly precipitated in cold acetone / ether (2:1), collected with centrifugation (15,000 g, 20 min) and dried with vacuum. The product, DOX-PEG-DOX (DPD) was purified with Sephadex G25 PD10 desalting column with water as eluent and then lyophilized.

Preparation of FiDOX and DexDOX Nanoparticles:

[0146]Fucoidan from Fucus vesiculosus (SIGMA) and DPD were both dissolved in double distilled water and were mixed together at a weight ratio of 1:1 and formed immediate gel aggregates. The aggregates were collected with centrifugation (15,000 g 10 min) and re-suspended in PBS containing excess of ×5 Fucoidan. The mixture was sonicated with a probe sonicator 40% intensity (sonics vibra-cell) for 10 sec until a clear dark red solution appe...

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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.

Description

CROSS REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit of U.S. Application Ser. No. 61 / 980,643 filed on Apr. 17, 2014, the disclosure of which is hereby incorporated by reference.GOVERNMENT SUPPORT[0002]This invention was made with government support under grant number DP2-HD075698 awarded by NIH. THE government has certain rights in the invention.TECHNICAL FIELD[0003]This invention relates generally to nanogels and methods of their manufacture and therapeutic use. In particular embodiments, the invention relates to polymeric fucoidan-based nanogel vehicles for the treatment of cancer and other diseases associated with P-selectin.BACKGROUND[0004]Nanogels—porous nanoscale hydrogel networks—are a class of nanomaterials with tunable chemical properties that facilitate targeting and delivery to specific tissues. They are intrinsically porous and can be loaded with small drugs or macromolecules by physical entrapment, covalent conjugation or controlled self-assem...

Claims

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Application Information

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IPC IPC(8): A61K31/737A61K41/00A61K31/337A61K49/00A61K31/704A61K47/48
CPCA61K31/737A61K31/704A61K47/48907A61K41/0038A61K31/337A61K49/00A61K47/48215A61K9/0019A61K9/5146A61K47/60A61K47/643A61K47/6935A61K9/5161A61K9/5169A61K31/4184A61K31/475A61K31/517A61K47/61A61K31/4412A61P35/00A61K47/64A61K47/585A61K47/6939A61K9/06A61K51/065
Inventor HELLER, DANIEL A.SHAMAY, YOSEF
Owner MEMORIAL SLOAN KETTERING CANCER CENT
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