Aug 072017

A microscopic image of endothelial cells treated with drug-loaded nanoparticles. (Image courtesy of the Saltzman Lab)

Using nanoparticles, Yale researchers have developed a drug-delivery system that could reduce organ transplant complications by hiding the donated tissue from the recipient’s immune system.

About 25,000 organ transplants are performed in the U.S. each year. Despite significant advances in the field, short-term and long-term organ rejection still poses a risk (rejection rates vary depending on the type of organ). The risk of rejection is even higher when the donor is deceased, due to organ damage.

T cells, the white blood cells that identify and attack foreign bodies, are one of the main culprits behind organ rejection. The most potent of these, known as effector memory T cells, are activated by a group of proteins known as human leukocyte antigens (HLAs) on the surface of endothelial cells lining the donated organ’s blood vessels. Researchers can silence the proteins with small interfering RNA (siRNA), a double-stranded RNA that hinders the expression of targeted genes. When delivered conventionally, however, the effects of siRNA last only a few days. A transplanted organ from a deceased donor typically needs weeks to “heal” and reduce the risk of rejection. The siRNA can also cause side effects in endothelial cells of other organs, which don’t need treatment, when administered to the whole body.

To give the siRNA more staying power, the researchers developed a drug delivery system in which polymer-based nanoparticles carry siRNA to the site of the graft and slowly release the drug. They also developed methods for introducing the nanoparticles into the donor organ before it is transplanted, so that only the organ is treated, not the whole body. The results of their work are published in the journal Nature Communications.

The particles — made in the Yale lab of Mark Saltzman, the Goizueta Foundation Professor of Chemical and Biomedical Engineering — can be tuned for specific properties. Saltzman, who is also a member of the Yale Cancer Center, said these nanoparticles were designed to have a slight positive charge to interact with the negative charge of the siRNA’s nucleic acid. This affinity between the two materials makes the particle a natural carrier for the drug, unlike commercially available nanoparticles that can hold only a limited amount of the drug.

For the study, the researchers treated part of a human artery — a few millimeters in diameter — with the siRNA-loaded nanoparticles and transplanted it into the abdominal aorta of an immune-deficient mouse inoculated with human T cells. The researchers found that the nanoparticles were still present in the donated tissue and significantly silenced the proteins’ expression up to six weeks after transplantation. Additionally, there was no damage to the endothelial cells of untargeted organs.

The first few weeks after the transplant are critical, especially when the organ donor is deceased, said Jordan Pober, the Bayer Professor of Translational Medicine and professor of immunobiology, pathology, and dermatology at Yale.

“If we delay the start of the rejection response, it should be milder and more easily controlled and lead to less late rejection,” said Pober, who is a co-author of the study and also director of Yale’s Human and Translational Immunology program.

Focusing on kidney transplants (by far the most common type of organ transplant performed), Saltzman and Pober are looking to apply the delivery system to a process known as ex vivo normothermic machine perfusion. Developed for kidneys by colleagues at Cambridge University, the process involves pumping warm, oxygenated red blood cells through an organ removed from a deceased donor to repair any damage to the organ before implanting it in the recipient. The Yale researchers plan to add the nanoparticles to the red blood cells to provide controlled delivery of the siRNA to the kidney’s endothelial cells.

Learn more: Nanoparticles trick body into accepting organ transplants


The Latest on: Nanoparticle-based drug-delivery system
  • Nanoparticle Size Analysis in Nanomedicine Applications
    on October 19, 2017 at 5:39 am

    Nanoparticle-based drug delivery systems offer an alternative method for targeting and then delivering therapeutic treatments to patients, and as a result, they have gained immense interest among drug developers in both academia and industry. Nanoparticle ... […]

  • Nanoparticle Size Analysis for Nanomedicine Applications
    on October 19, 2017 at 3:31 am

    Nanoparticle-based drug delivery systems provide an alternative method for targeting and delivering therapeutic treatments to patients, and as a result they hold a great deal of interest to drug developers in both academia and industry. Nanoparticle-based ... […]

  • Nanotechnology for neuroscience
    on October 18, 2017 at 3:42 am

    The collaboration between nanotechnology and neuroscience, though still at the early stages, utilizes broad concepts, such as drug delivery, cell protection ... representation of different types of nanoparticle-based platforms and their roles in ... […]

  • Nanomedical Devices Market to Register High Demand Rate of 10.29% by 2023
    on October 13, 2017 at 7:19 am

    Whereas, lack of regulatory standards in the examination of nanoparticle based medicines and high cost of the treatment ... implantable cardioverter-defibrillators, implantable drug delivery system and others. On the basis of application they are segmented ... […]

  • Introduction for Design of Nanoparticle Based Drug Delivery Systems.
    on October 8, 2017 at 5:00 pm

    In order to overcome the drawbacks of conventional pathway of drug delivery, nanoparticle delivery systems are therefore designed and used as the drug carriers. Nanoparticle based drug delivery systems have been rapidly growing and are being applied to ... […]

  • Nanotechnology used to deliver drugs directly to uterus, potentially reducing delivery complications
    on September 2, 2016 at 7:22 am

    Nanotechnology has been successfully ... "What we have developed is a targeted drug delivery system for the human uterus," he said. "And essentially what this is a nanoparticle-based drug delivery system, we've come up with a way of ensuring that those ... […]

  • InMed Commences Development of Proprietary Drug Delivery System
    on September 1, 2015 at 5:00 pm

    VANCOUVER, BRITISH COLUMBIA--(Marketwired - Sep 2, 2015) - InMed Pharmaceuticals Inc. ("InMed") (CSE:IN)(OTCQB:IMLFF) is pleased to announce it has initiated testing of a novel nanoparticle based delivery system for INM-750 which will be used for clinical ... […]

  • A targeted approach to cancer imaging and therapy
    on January 22, 2014 at 4:00 pm

    the biggest barrier to commercialization of nanoparticle-based imaging agents is their development cost. Nanoparticles for the sole use of imaging agents have a much lower return on investment and higher safety requirements than drug delivery systems ... […]

  • Nanoparticle-Based Therapy Targets Deadly Brain Tumor
    on July 2, 2013 at 4:17 am

    These migrating cells can avoid the drugs and regrow under normal conditions. The new drug delivery system sends drugs directly at the site, increasing the rate at which cancer cells are killed. "We wanted to make a system that would penetrate into the ... […]

via Google News and Bing News

Other Interesting Posts

Leave a Reply

%d bloggers like this: