Tag Archives: arthritis

Alleviating joint damage and inflammation from arthritis with neutrophil nanosponges

Assuming you’d be happy with limiting the damage for rheumatoid arthritis, at some point in the future, this research looks promisin. Right now it appears the researchers aren’t anywhere close to a clinical trial. From a Sept. 3, 2018 news item on ScienceDaily,

Engineers at the University of California San Diego [UCSD] have developed neutrophil “nanosponges” that can safely absorb and neutralize a variety of proteins that play a role in the progression of rheumatoid arthritis. Injections of these nanosponges effectively treated severe rheumatoid arthritis in two mouse models. Administering the nanosponges early on also prevented the disease from developing.

A Sept. 3, 2018 UCSD press release (also on EurekAlert), which originated the news item, provides more detail,

“Nanosponges are a new paradigm of treatment to block pathological molecules from triggering disease in the body,” said senior author Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering. “Rather than creating treatments to block a few specific types of pathological molecules, we are developing a platform that can block a broad spectrum of them, and this way we can treat and prevent disease more effectively and efficiently.”

This work is one of the latest examples of therapeutic nanosponges developed by Zhang’s lab. Zhang, who is affiliated with the Institute of Engineering in Medicine and Moores Cancer Center at UC San Diego, and his team previously developed red blood cell nanosponges to combat and prevent MRSA infections and macrophage nanosponges to treat and manage sepsis.

neutrophil nanosponge cartoon
Illustration of a neutrophil cell membrane-coated nanoparticle.

The new nanosponges are nanoparticles of biodegradable polymer coated with the cell membranes of neutrophils, a type of white blood cell.

Neutrophils are among the immune system’s first responders against invading pathogens. They are also known to play a role in the development of rheumatoid arthritis, a chronic autoimmune disease that causes painful inflammation in the joints and can ultimately lead to damage of cartilage and bone tissue.

When rheumatoid arthritis develops, cells in the joints produce inflammatory proteins called cytokines. Release of cytokines signals neutrophils to enter the joints. Once there, cytokines bind to receptors on the neutrophil surfaces, activating them to release more cytokines, which in turn draws more neutrophils to the joints and so on.

The nanosponges essentially nip this inflammatory cascade in the bud. By acting as tiny neutrophil decoys, they intercept cytokines and stop them from signaling even more neutrophils to the joints, reducing inflammation and joint damage.

These nanosponges offer a promising alternative to current treatments for rheumatoid arthritis. Some monoclonal antibody drugs, for example, have helped patients manage symptoms of the disease, but they work by neutralizing only specific types of cytokines. This is not sufficient to treat the disease, said Zhang, because there are so many different types of cytokines and pathological molecules involved.

“Neutralizing just one or two types might not be as effective. So our approach is to take neutrophil cell membranes, which naturally have receptors to bind all these different types of cytokines, and use them to manage an entire population of inflammatory molecules,” said Zhang.

“This strategy removes the need to identify specific cytokines or inflammatory signals in the process. Using entire neutrophil cell membranes, we’re cutting off all these inflammatory signals at once,” said first author Qiangzhe Zhang, a Ph.D. student in Professor Liangfang Zhang’s research group at UC San Diego.

To make the neutrophil nanosponges, the researchers first developed a method to separate neutrophils from whole blood. They then processed the cells in a solution that causes them to swell and burst, leaving the membranes behind. The membranes were then broken up into much smaller pieces. Mixing them with ball-shaped nanoparticles made of biodegradable polymer fused the neutrophil cell membranes onto the nanoparticle surfaces.

“One of the major challenges of this work was streamlining this entire process, from isolating neutrophils from blood to removing the membranes, and making this process repeatable. We spent a lot of time figuring this out and eventually created a consistent neutrophil nanosponge production line,” said Qiangzhe Zhang.

In mouse models of severe rheumatoid arthritis, injecting nanosponges in inflamed joints led to reduced swelling and protected cartilage from further damage. The nanosponges performed just as well as treatments in which mice were administered a high dose of monoclonal antibodies.

The nanosponges also worked as a preventive treatment when administered prior to inducing the disease in another group of mice.

Professor Liangfang Zhang cautions that the nanosponge treatment does not eliminate the disease. “We are basically able to manage the disease. It’s not completely gone. But swelling is greatly reduced and cartilage damage is minimized,” he said.

The team hopes to one day see their work in clinical trials.

Here’s a link to and a citation for the paper,

Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis by Qiangzhe Zhang, Diana Dehaini, Yue Zhang, Julia Zhou, Xiangyu Chen, Lifen Zhang, Ronnie H. Fang, Weiwei Gao, & Liangfang Zhang. Nature Nanotechnology (2018) DOI: https://doi.org/10.1038/s41565-018-0254-4 Published 03 September 2018

This paper is behind a paywall.

Recycling apples to regenerate bone and cartilage tissue

A March 30, 2017 news item on phys.org announces research utilizing apple waste as a matrix for regenerating bones and cartilage,

Researchers from UPM and CSIC [both organizations are in Spain] have employed waste from the agri-food industry to develop biomaterials that act as matrices to regenerate bone and cartilage tissues, which is of great interest for the treatment of diseases related to aging.

The researchers have produced biocompatible materials from apple pomace resulting from juice production. These materials can be used as 3-D matrices for the regeneration of bone and cartilage tissues, useful in regenerative medicine for diseases such as osteoporosis, arthritis or osteoarthritis, all of them rising due to the increasing average age of the population.

A March 30, 2017 Universidad Politécnica de Madrid (UPM) press release, which originated the news item,, expands on the theme,

Apple pomace is an abundant raw material. The world production of apples was more than 70 million tons in 2015, of which the European Union contributed with more than 15%, while half a million tons of which came from Spain. About 75% of apples can be converted into juice and the rest, known as apple pomace, that contains approximately 20–30% dried matter, is used mainly as animal feed or for compost. Since apple pomace is generated in vast quantities and contains a large fraction of water, it poses storage problems and requires immediate treatments to prevent putrefaction. An alternative of great environmental interest is its transformation into value added commodities, thus reducing the volume of waste.

The procedure of the multivalorization of apple pomace carried out by the UPM and CSIC researchers are based on sequential extractions of different bioactive molecules, such as antioxidants or pectin, to finally obtain the waste from which they prepare a biomaterial with suitable porosity and texture to be used in tissue engineering.

The primary extraction of antioxidants and carbohydrates constitutes 2% of the dry weight of apple pomace and pectin extraction is 10%. The extracted chemical cells have a recognized value as nutraceuticals and pectin is a material of great utility in different medical applications, given its high biocompatibility and being part of antitumor drugs or in the treatment of coetaneous wounds.

Furthermore, it has been found that the materials remaining after antioxidant and pectin removal from apple pomace can still be designed with adequate structure, texture and composition to grow diverse types of cells. In this particularly case, the chosen cells were osteoblasts and chondrocytes, both of them related to the regeneration of bone and cartilage tissues because of their application in regenerative medicine in diseases such as osteoporosis, arthritis or osteoarthritis.

Today, there are products in the market with the same applications, however they have a high price reaching over €100 per gram, while waste used in this work hardly reaches €100 per ton. For this reason, there are consistent incentives to convert this waste into final products of great added value.

According to Milagro Ramos, a female researcher of the study, “with this approach we achieve a double goal, firstly using waste as a renewable raw material of high value and chemical diversity, and secondly, to reduce the impact of such waste accumulation on the environment”.

Thanks to the new materials obtained in this work, researchers are developing new technological applications that allow them to structure customized biomaterials through 3D printing techniques.

Here’s a link to and a citation for the paper,

Multivalorization of apple pomace towards materials and chemicals. Waste to wealth by Malcolm Yates, Milagros Ramos Gomez, Maria A. Martin-Luengo, Violeta Zurdo Ibañez, Ana Maria Martinez Serrano. Journal of Cleaner Production Volume 143, 1 February 2017, Pages 847–853  http://doi.org/10.1016/j.jclepro.2016.12.036

This paper is behind a paywall.

Arbro Pharmaceuticals and its bioavailable curcumin

Curcumin (a constituent of the spice turmeric) is reputed to have health benefits and has been used in traditional medicine in Asia (notably India) for millenia. Recently scientists have been trying to render curcumin more effective which means increasing its bioavailability (my Nov. 7, 2014 posting features some of that research). According to an April 29, 2016 Arbro Pharmaceuticals press release, the goal of increased bioavailability has been reached and a product is now available commercially,

Arbro Pharmaceuticals has launched SNEC30, a patented highly bioavailable self-nanoemulsifying curcumin formulation in the dosage of 30mg.

Curcumin is the active ingredient of turmeric or haldi, which has been widely used in traditional medicine and home remedies in India for hundreds of years.

Clinical research conducted over the last 25 years has shown curcumin to be effective against various diseases like cancer, pain, inflammation, arthritis, ulcers, psoriasis, arteriosclerosis, diabetes and many more pro-inflammatory conditions.

Despite its effectiveness against so many medical conditions, scientists have come to believe that curcumin’s true potential has been limited by its poor bioavailability which is caused by the fact that it has poor solubility and extensive pre-systemic metabolism.

Arbro Pharmaceuticals partnered with Jamia Hamdard University to carry out research and develop a novel formulation, which can overcome curcumin’s poor bioavailability. The development project was jointly funded by Arbro and the Department of Science and Technology, Government of India under its DPRP (Drug and Pharmaceutical Research Programme) scheme.

SNEC30 is the outcome of this joint research and is based on a novel self-nanoemulsifying drug delivery systems (SNEDDS) for which patents have been filed and the US patent has been granted.

“There has been tremendous interest in the therapeutic potential of curcumin but its poor bioavailability was a limiting factor, our research group together with Arbro took the challenge and applied nanotechnology to overcome this limitation and achieve highest ever bioavailability for curcumin,” said Dr. Kanchan Kohli, Asst. Prof, Faculty of Pharmacy, Jamia Hamdard University, who is one of the main developers of the formulation.

Nanotechnology is the engineering of functional systems at the molecular scale (CRN – Centre for Responsible Nanotechnology). The name stems from the fact that the structures are in the nano-metre (10-9 mm) in range. In pharmaceutics, nano-formulations are used for targeted drug-delivery, particularly in cancer therapy. It also finds numerous other applications in medicine.

“Just 30mg of curcumin that is contained in one capsule of SNEC30 has shown higher blood levels than what can be achieved by consuming the curcumin content of 1kg of raw haldi or turmeric,” said Mr. Vijay Kumar Arora, Managing Director, Arbro Pharmaceuticals.

About Arbro Pharmaceuticals:

Arbro Pharmaceuticals is a 30-year-old research oriented company with its own research and development, testing and manufacturing facilities. Arbro has been manufacturing and exporting hundreds of formulations under its own brand name to more than 10 countries.

I am not endorsing this product but if you are interested the SNEC30 website is here. I believe Arbro Pharmaceuticals’ headquarters, the company which produces SNEC30, are located in India.