Edds chelated nanoceria with catalase-like activity

Abstract

A process for making nanoparticles of biocompatible materials, wherein an aqueous reaction mixture comprising cerous ion, ethylenediaminedisuccinic acid, an oxidant, water, and optionally citric acid, is provided along with temperature conditions to directly form within the reaction mixture, a stable dispersion of cerium oxide nanoparticles. Also, biocompatibe nanoparticles comprised of cerium oxide, ethyenediaminedisuccinic acid, and optionally citric acid. An increase in catalase-like enzyme activity is demonstrated by cerium oxide nanoparticles prepared with citric acid and ethylenediaminedisuccinic acid.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This patent application is a Divisional application of U.S. application Ser. No. 15 / 545,065, filed Jul. 20, 2017, which is a U.S. National Phase application of PCT International Application No. PCT / US16 / 014076, filed Jan. 20, 2016, which claims priority of U.S. Provisional Patent Application Ser. No. 62 / 125,381, filed Jan. 20, 2015, the disclosures of which are incorporated herein by reference in its their entirety.FIELD OF THE INVENTION[0002]The present invention relates in general to improvements in the fields of nanoscience and nanomedicine. In particular, the invention relates to methods of preparing nanoparticles, to nanoparticles comprising biocompatible materials, and to nanoparticles with catalase-like activity. The invention also relates the use of such nanoparticles to catalyze the elimination of hydrogen peroxide, or to prevent or to treat disease, more particularly, to reduce the effects of oxidative stress due to hydrogen per...

AI Technical Summary

Benefits of technology

The invention provides a process for making a dispersion of nanoparticles of cerium oxide using a specific mixture of ingredients. The nanoparticles can be used in the prevention and treatment of oxidative stress-related diseases such as multiple sclerosis and amyotrophic lateral sclerosis. The cerium oxide nanoparticles have the added benefit of being able to easily cross the blood-brain barrier, making them more effective in treating these diseases. The technical effect of this invention is that it provides a simple process for making a stable dispersion of cerium oxide nanoparticles that can be used to prevent and treat oxidative stress-related diseases.

Problems solved by technology

Nanoceria produced by the reverse micelle micro emulsion technique suffered as follows: (1) particle size was not well-controlled within the reported 210 nanometer (nm) range, making variability between batches high; (2) tailing of surfactants, such as sodium bis(ethylhexyl)suiphosuccinate, also known as docusate sodium or (AOT), used in the reverse micelle synthetic process into the final product caused toxic responses; (3) inability to control the amount of surfactant tailing posed problems with agglomeration when these nanoparticles were placed in biological media, resulting in reduced efficacy and deliverability; and (4) instability of the valence state of cerium (+3 / +4) over time.

Thus, the cerium oxide nanoparticles produced by the reverse micelle micro emulsion technique were highly variable from batch to batch, and showed higher than desired toxicity to mammalian cells.

However, we have confirmed what others have observed, that sonicated aqueous dispersions of nanoceria (synthesized by high temperature techniques and obtained from commercial sources) are highly unstable, and settle rapidly (i.e. within minutes), causing substantial variability in administering aqueous dispersions of nanoceria derived from these sources.

We have also observed that administration of these sonicated aqueous dispersions of nanoceria (e.g. obtained from Sigma-Aldrich) to mice result is rapid deposition of ceria in the liver and kidneys along with rapid decline in the health of the animals.

However, this process is both time and equipment intensive, requiring two separate 24 hours reaction steps in closed reactors.