Researchers from John Hopkins have developed a star-shaped device that can latch onto intestinal mucosa and release drugs into the body more efficiently.
Routes of drug administration
Administering drugs through the gastrointestinal (GI) tract offers improved compliance over injectables and thus leads to better treatment outcomes. Drugs administered via the GI tract are more efficiently absorbed into systemic circulation. This is partly due to the large intestinal surface area and rich vascularisation within the GI tract mucosa.
Oral routes of drug administration are generally the preferred form across all age groups, whereas the rectal route is better in paediatric populations and during medical emergencies. Nonetheless, these routes often result in imperfect adherence to treatment, resulting in an annual waste of more than $600 billion globally. There is an imperative need to develop orally or rectally administered extended drug delivery systems.
For example, buccal patches (a mucoadhesive system) can extend residence time to 5 or 6 hours, after which they are removed due to weak mucosal adhesion. Mucus-penetrating particles (MPPs) have shown improved retention compared to mucoadhesive systems in mouse models. However, these particles are also removed after a day due to clearance of the underlying mucus layer. As a result, attention has turned to devices that rely on the variations in density or large size to avoid elimination from the stomach.
In this study, published in Science Advances, researchers presented their hookworm-inspired multiclawed device with sharp microtips that can latch onto mucosal tissue. Hookworms such as Ancylostoma duodenale can reside in the human intestine for up to two years. They insert two pairs of ventricular teeth into the tissue which allows them to latch on and resist clearance by GI motility.
Dr Florin M. Selaru, Gastroenterologist and Director of the Johns Hopkins Inflammatory Bowel Disease Center, stated:
“Normal constriction and relaxation of GI tract muscles make it impossible for extended-release drugs to stay in the intestine long enough for the patient to receive the full dose.
We’ve been working to solve this problem by designing these small drug carriers that can autonomously latch onto the intestinal mucosa and keep the drug load inside the GI tract for a desired duration of time.”
The team presented the first preclinical evidence demonstrating that these star-shaped devices, called theragrippers, can enhance drug release and retention in vivo. These devices are made of metal and thin, shape-changing film. The grippers are also coated in a heart-sensitive paraffin wax. These close autonomously and clamp onto the colonic wall when they reach body temperature. Thousands of these dust-sized theragrippers can be deployed into the GI tract.
The researchers investigated delivery of ketorolac (pain reliever) as a model drug. They found that the theragrippers were retained in the colon for 23 hours. Additionally, they resulted in significantly higher exposure to the drug. They observed a notable sixfold increase in the elimination half-life using theragripper-mediated delivery. These results are an exciting step towards extended release of drugs – a long-sought goal in medicine.
Image credit: By Image Team – canva.com