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Anti-Inflammatory, Radioprotective, and Longevity Enhancing Capabilities of Cerium Oxide Nanoparticles

a technology of cerium oxide and nanoparticles, applied in the field of nanoparticles, can solve the problems of high variability between batches, uncontrollable particle size, and difficulty in the process of sonic gel, and achieve the effect of prolonging the life of living cells, reducing or eliminating damage to cells

Inactive Publication Date: 2010-07-01
EDWARD VIA VIRGINIA COLLEGE OF OSTEOPATHIC MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]The present invention addresses this need in the art by providing a method for the use of cerium oxide nanoparticles in health. As a general matter, the method extends the life of a living cell by exposing the cell to cerium oxide nanoparticles. This exposure reduces or eliminates damage to the cell caused by endogenous and exogenous free radicals. The cerium oxide nanoparticles can be exposed to the cell before, during, or after free radical damage.
[0009]Broadly speaking, the present invention provides a method of treating at least one cell with cerium oxide particles. The method generally comprises contacting at least one cell with an amount of cerium oxide nanoparticles that reduces or eliminates damage caused by free radicals. The method can be practiced in vivo as either a therapeutic method of treating a disease or disorder involving free radicals or as a prophylactic method to prevent free radical damage. Likewise, the method can be practiced in vitro as a research tool to study the effects of free radicals on cells or the effects of combinations of nanoparticles with drugs on cells. In preferred embodiments, the method is practiced with size-limited cerium oxide nanoparticles made by a method other than a sol-gel method. The method can also be practiced ex vivo or in vitro for therapeutic or research purposes.

Problems solved by technology

However, the sol-gel process posed several difficulties.
For example, particle size was not well-controlled within the reported 2-10 nm range, making variability between batches high.
That is, the process, while satisfactory for producing nanoparticles with free radical scavenging activity, did not reproducibly produce particles of a specific size range.
In addition, the process resulted in tailing of surfactants used in the process into the final product.
The presence of these surfactants produced biological difficulties when used, primarily due to the toxicity of the surfactants in the product.
Furthermore, the inability to control the amount of surfactant tailing posed problems with agglomeration when nanoparticles were placed in biological media.
These difficulties reduced particle efficacy and biological deliverability.
Removal of surfactant after sol-gel synthesis produced particles that appeared prone to agglomeration in biological media, and had a lack of biological effects.
Further, difficulties were encountered with changes in valence state of cerium associated with these particles, causing alterations in the ratio of valence states of cerium (+3 / +4) that occurred over time, particularly when particles were placed in biological media.

Method used

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  • Anti-Inflammatory, Radioprotective, and Longevity Enhancing Capabilities of Cerium Oxide Nanoparticles
  • Anti-Inflammatory, Radioprotective, and Longevity Enhancing Capabilities of Cerium Oxide Nanoparticles
  • Anti-Inflammatory, Radioprotective, and Longevity Enhancing Capabilities of Cerium Oxide Nanoparticles

Examples

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Effect test

example 1

Extension of Cell and Organism Longevity

[0079]A single 10 nM dose of cerium oxide nanoparticles extended the life span of cultured rat brain cells (neurons, astrocytes, microglia) from 28 to 182 days (6 months). For delivery, the nanoparticles were in a non-agglomerated form. To accomplish this, stock solutions of about 10% by weight were sonicated in ultra-high purity water (16 megaohms) or in normal saline prepared with ultra high purity water. Stocks were sonicated with a probe sonicator for 3 minutes. Dilutions were made, beginning with 10 mM, down to 100 nM or lower. No phosphate or other ionic buffers were used because these were found to increase agglomeration. All serial dilutions were sonicated for 3 minutes prior to use or to further dilution. Importantly, aged neurons and astrocytes were functionally equivalent to their younger, untreated, counterparts. Neurotransmission in response to glutamate, GABA, and acetylcholine in cerium oxide nanoparticle-treated aged cultures w...

example 2

Free Radical Scavenging Capacity of Cerium Oxide Nanoparticles

[0082]Given the structure of cerium oxide nanoparticles, we hypothesized that cerium oxide nanoparticles promoted cell longevity by acting as free radical scavengers. To test this hypothesis, we exposed cultured brain cells to lethal and sub-lethal doses of the free radical generating agents, hydrogen peroxide, and UV light. Exposure to cerium oxide nanoparticles afforded significant protection against both of these free radical generating agents, and reduced cell death in excess of 60%. Protection against UV and hydrogen peroxide-mediated injury was preserved in 3 month old cultures that had been treated with cerium oxide nanoparticles on day 10 in culture. Thus, the effects of cerium oxide nanoparticles are long-lasting, following a single dose.

[0083]Studies comparing the effects of cerium oxide nanoparticles to the traditional free radical scavengers Vitamin E, melatonin, and N-acetyl-cysteine demonstrated that only ce...

example 3

Toxicity and Biodistribution

[0086]Using electron microscopy, microspectrophotometry, and inductively coupled plasma mass spectrometry, we found that cerium oxide nanoparticles of size less than 20 nm readily enter cultured cells and cells of living organisms. Further, doses as high as 100-fold of that which extend cell culture lifespan exhibited no overt toxicity in Drosophila. A single tail vein injection of 0.3-3 mM in the mouse produced no overt organ or behavioral abnormalities. Cerium oxide nanoparticles were found to accumulate preferentially in brain, heart, and lung with little excretion over a 6 month time period. At the 0.3 mM dose, tissue cerium levels approximately doubled (as compared to background), but remained in the parts per billion range.

[0087]FIG. 4 depicts the results of tissue cerium measurements of mice treated with nanoparticles. More specifically, Balb / c mice were administered 5-10 ul tail vein injections each containing 300 nmoles cerium oxide nanoparticles...

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Abstract

The present invention provides cerium oxide nanoparticles for use both in therapeutic compositions in vivo and in research in vitro. The cerium oxide nanoparticles are of a known range of sizes having biological properties that are reproducible and beneficial. Pharmaceutical and other compositions are provided, as are methods of treatment.

Description

STATEMENT OF GOVERNMENT INTEREST[0001]This invention was made partially with U.S. Government support from the United States National Institutes of Health under Contract No. NS40490 (National Institute of Neurological Disorders & Stroke) and AG022617 (National Institute on Aging). The U.S. Government has certain rights in the invention.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention relates to the field of medicine and treatment of medically relevant diseases, disorders, and complications of injury, inflammation, and aging. More specifically, the invention relates to the use of nanoparticles to treat subjects suffering from various diseases, disorders, and complications due to injury, inflammation, radiation exposure, and aging.[0004]2. Description of Related Art[0005]Many approaches have been taken to treat, either therapeutically or prophylactically, diseases, disorders, and other medically important conditions that have, as a major component, ...

Claims

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Application Information

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IPC IPC(8): A61F2/30B32B5/00A61K9/14A61K33/24C12N5/00A61K35/12A61K35/14C12Q1/02A61P29/00A61P43/00A61P39/00A61K33/244
CPCA61K9/14Y10T428/2982A61L27/306A61K33/24A61P17/02A61P17/18A61P19/02A61P25/00A61P25/16A61P25/28A61P29/00A61P37/00A61P37/08A61P39/00A61P39/06A61P43/00A61P9/00A61P9/06A61P9/10A61P3/10A61K33/244
Inventor RZIGALINSKI, BEVERLY A.CLARK, ARIANE M.
Owner EDWARD VIA VIRGINIA COLLEGE OF OSTEOPATHIC MEDICINE
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