Hookworms: Tiny Teeth for Futuristic Drug Delivery
By: Kathryn Hamilton
Tags: Biology, Science, Biotechnology, Research, Innovation

INNOVATION

Hookworms: Tiny Teeth for Futuristic Drug Delivery

Worms are helpful and necessary creatures that also happen to make the majority of the general population squeamish. I personally think their relationship with early birds and recreational fishing habits seems a little unfair. Hookworms are a different story. These intestinal parasites enjoy humanity as their host of choice. Often they live and reproduce undetected in the intestines after larvae are either ingested or allowed to penetrate human skin after a person walks barefoot on contaminated soil. The risk of contracting hookworm increases in warm and moist climates when proper sanitation is not available. Soil can be contaminated when infected human feces are incorporated into fertilizers or not properly disposed of.

This is the lifecycle of an intestinal hookworm. A. duodenale and N. americanus are considered the two primary intestinal hookworm species in the world. In some cases, the A. duodenale hookworm larvae can go dormant in the infected person’s muscle or intestines for a period of time and then create new infections. Picture from the CDC.

Mild symptoms of hookworm infections are a localized rash and itching and more serious infections might include abdominal pain, diarrhea, fatigue, and anemia. These creatures are often especially detrimental to children since both their physical and cognitive growth can be affected. Modern medicine is quite effective at treating hookworm infections however, the CDC estimates that between 576–740 million people around the globe are actively infected with hookworm.

Looking at these creatures objectively, they are more burdensome than they are helpful. However, a group of scientists at Johns Hopkins University is looking to the hookworm for inspiration in treating human diseases.

This is the Ancylostoma duodena hookworm. These worms can live in the intestines of a human for up to two years due to the ventricular teeth shown. Picture by Jay Reimer.

This was a joint effort between Dr. Florin M. Selaru, director of the Johns Hopkins Meyerhoff Inflammatory Bowel Disease Center, and Dr. David Gracias, a professor in the Johns Hopkins University Whiting School of Engineering. A paper published in the October edition of Science Advances showcases their work. Many drugs today are designed to be absorbed by the gastrointestinal tract. Dr. Selaru shared that GI tract motility can be likened to an assembly line that is constantly moving so things are regularly eliminated. Looking for a way to increase the retention time of drug-releasing devices, these scientists used the mouth and teeth of the A. duodena hookworm to inspire the design of tiny microdevices called theragrippers. These theragrippers are very small, visible to the naked eye similar to that of dust particles. These devices have sharp microtips that allow them to latch onto the innermost layer of the intestines, the mucosa of the lumen. At the center of these microdevices is a specific amount of a drug that can be released and absorbed by the intestines.

This is an image of a theragripper. The sharp microtips seen here allow for adhesion to the small intestine, colon, or esophagus. The theragrippers were designed intentionally in their composition, so as to avoid a negative interaction with the immune systems of both the test animals and humans in the future. Image provided by Dr. Arijit Ghosh.

The theragrippers which are made of thin films of gold and chromium are biocompatible and do not result in any immune response in the animal studies performed. In the future, we intend to improve the design parameters of the gripper, to enhance the retention time in the GI tract for several days -Dr. Arijit Ghosh, first author of the study, Assistant Research Assistant, Chemical and Biomolecular Engineering, Johns Hopkins University

In the scope of this study, the viability of this drug delivery system was tested in rats and in pigs. The study reports that upon inspection of the GI tract tissue of these animals, there was no damage done by the theragrippers. In addition, the theragrippers were able to stay in the GI tract for about 24 hours which significantly increased the amount of exposure and absorption of the model drug ketorolac. Ketorolac is often used after surgery to relieve moderately severe pain and comes from the same family of drugs as ibuprofen and naproxen.

I was curious about how doctors could ensure that the theragrippers adhered in the right location. Dr. Selaru shared that the potential solution already exists in the form of modern-day medicine capsules. Many over the counter medications are designed to be taken orally and remain intact through the acid in your stomach, to be absorbed further down in your GI tract. Thousands of theragrippers could be delivered to your intestines using those same pH-dependent capsules. The study also highlights that due to variability in human behavior, prescribed drug regimens are often inconsistently followed. This leads to a significant amount of waste that costs about $600 billion annually around the globe. By creating a novel physical drug delivery system that is significantly more effective than what is currently available, you increase adherence to vital prescriptions while actively working to reduce the financial and medicinal waste that humans currently create.

This is a near-perfect example of biotechnology as humanity’s highest art form.

This group of researchers took a tool of survival that independently exists in nature — that is often debilitating for humans—and repurposed it as a method, to in the future, make them well. And just like art challenges us to elevate our thinking, this collaboration with nature addresses the significant waste we create and provides a pathway for humanity to do better.

You see different things over your life and often it registers and then you move on. And then at some point your are looking for a solution to something and then it clicks. Its not a straight line that’s for sure, you keep accumulating and thinking about things and then you figure that hey this might work. -Dr. Florin M. Selaru, director of the Johns Hopkins Meyerhoff Inflammatory Bowel Disease Center

Now it is important to note that this technology is several years away from the market. For these microdevices to be used in humans, they must undergo rigorous testing in clinical trials before approval by the FDA. But I am personally very encouraged by the ingenuity of this science and its potential for impact. You can dive into the details of their study by reading the full journal article published in Science Advances.

Want to talk about biotechnology or bioeconomy innovation? Let’s connect! Working on some cool science you think is essential to the conversation? Leave me a comment below! Also, make sure you check out this other interesting article: