Posted in | Nanomedicine

Scientists Develop Nanoparticle Carriers to Treat Connective Tissue Disorders

Professor Kristi Kiick from the University of Delaware (UD) is heading a collaborative study to develop new drug delivery systems that can enhance treatment for various diseases, like osteoarthritis or the autoimmune disease rheumatoid arthritis, that impact connective tissues.

UD’s Kristi Kiick and colleagues are working to program novel drug carrier systems capable of delivering pain relief over varying timescales and temperatures. The researchers have the right material structure. Now they are exploring ways to trigger the system to release specific medications under particular conditions, such as by heating or cooling. Image Credit: University of Delaware.

Tiny cargo-carrying systems, developed by the UD team, are several times smaller than a strand of human hair. Such carriers, or systems, are created from molecules—known as peptides—that help give structure to both tissues and cells.

The researchers are currently looking for ways to program these nanoparticle carriers so that these drug carriers can be selectively attached to the decomposing collagen in the body.

Collagen is a kind of protein that helps plump up or give structure to the connective tissue—everything from the humans’ skin to their ligaments, tendons, and bones.

When an injury or disease causes the degradation of collagen, the nanoparticles developed by the Kiick laboratory can bind and continue to remain at the site of injury much longer than several existing treatment options. This makes it possible to deliver site-specific drugs across extended periods of time—from days to even weeks.

In a collaborative study that involves the latest research work, Kiick is attempting to create drug carriers that may prove handy in treating osteoarthritis.

Osteoarthritis is essentially a degenerative joint disorder that is accompanied by pain, stiffness, and inflammation. This disorder impacts 32.5 million Americans, reported the Centers for Disease Control and Prevention.

Previous studies performed together with Christopher Price, an associate professor in biomedical engineering, indicated that it is possible to retain these nanoparticles in knee joints and tissues. In other similar research works, Kiick and her students have demonstrated that medications can be encapsulated and held in the nanoparticles until they are discharged by temperature variations.

We are interested in learning how to release drugs that can help not just with pain management, but also with slowing down disease progression. It has been key that we have been able to collaborate with the Price laboratory in this type of work.

Kristi Kiick, Blue and Gold Distinguished Professor of Materials Science and Engineering, University of Delaware

Small molecule corticosteroids have long been a standard of care for controlling pain in osteoarthritic joints. Since the joint is under continuous mechanical stress and motion and is also full of thick, sticky fluid, the small-molecule drugs are pushed from the fluid around the knee quite rapidly, in minutes.

We are hopeful that by controlling the nanoparticle composition and structure, we will be able to finely control, or tune, the drug delivery behavior to provide longer-lasting relief for people with inflammatory conditions, such as osteoarthritis.

Kristi Kiick, Blue and Gold Distinguished Professor of Materials Science and Engineering, University of Delaware

Kiick and her collaborators have reported the developments on the nanoparticle design in a study published in Science Advances—a peer-reviewed journal of the American Association for the Advancement of Science—on October 7th, 2020. 

The study’s co-authors include Jingya Qia, a graduate student in the Kiick lab, and Jennifer Sloppy, a senior microscopy specialist in the Harker Interdisciplinary Science and Engineering Laboratory at UD.

The important findings of the study demonstrate the ability of the researchers to regulate the shape of the nanoparticles, which will affect the way these particles can optimally attach to the body’s tissue and remain in a specific site.

Apart from this, the researchers can accurately regulate the size of the nanoparticles, which holds implications for how they might be held at the site of injection and how they may be utilized by specific cells before they are eliminated from the body.

Last but not the least, the article also demonstrates some of the very fine details of how the particular building blocks within these peptide molecules can influence the temperature at which nanoparticles of different shapes and sizes can be disassembled to discharge a drug.

The study builds on Kiick’s earlier patented and patent-pending research work in this field, but according to her, collaboration with others is primarily responsible for advancing the promising results. 

While the researchers in Kiick’s lab bring their know-how in developing innovative materials that can be employed as delivery systems, Arthi Jayaraman, Centennial Term Professor for Excellence in Research and Education in the Department of Chemical and Biomolecular Engineering, is also supporting them to understand factors associated with the temperature sensitivity of the delivery vehicles and to create computational tools that can allow the team to define the shape of the delivery vehicle.

In the meantime, Price’s know-how in interpreting post-traumatic osteoarthritis has been crucial to designing techniques through which these nanoparticles can possibly be used for treating the disease.

Price is also exploring ways to understand the interaction between specific drugs and cells, which may inform the type of specific groups of drugs that may prove handy in treating osteoarthritis that generally develops after traumatic injury. The partnership will allow the Kiick lab to customize the types of nanoparticle devices that can be used for delivering these varied classes of drugs.

Thinking big, Kiick believes that the researchers can envisage loading a custom-made cocktail of drugs into the drug-delivering nanoparticles that can provide relief over different temperatures and timescales.

The team already has the right material nanostructure that can make this method a reality; at present, they are exploring ways to activate the nanoparticles to discharge specific drugs under specific conditions.

You could imagine injecting these encapsulated medications at the knee. Then, when you want one medication to be released, the patient could ice their knee. If another drug is needed to provide relief over a longer time-period, heat could be applied.

Kristi Kiick, Blue and Gold Distinguished Professor of Materials Science and Engineering, University of Delaware

It could truly be a simple way to help individuals control chronic conditions that cause a great deal of pain and decrease mobility. And since the treatment is local, it can potentially decrease the side effects that accompany when high doses of medications have to be taken over extended periods of time.

If these delivery vehicles could reduce painful effects of osteoarthritis, or delay when osteoarthritis symptoms emerge, there could be important implications for improving quality of life for many people,” Kiick concluded. 

Journal Reference:

Qin, J., et al. (2020) Fine structural tuning of the assembly of ECM peptide conjugates via slight sequence modifications. Science Advances. doi.org/10.1126/sciadv.abd3033.

Source: https://www.udel.edu/

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