Injected arthritic drugs often get stuck in the sticky synovial fluid found between the joints, but tiny nanomotors may help liberate them.
Researchers are taking an unconventional approach to drug delivery, employing microscopic nanomotors to transport arthritis medication through the fluid between our joints to help treat damaged cartilage.
“We want to increase the efficiency of arthritis treatments,” said Samuel Sanchez, professor at the Institute of Bioengineering of Catalonia, Spain and lead author of the study. “Overcoming biological barriers, that’s the importance.”
The barriers Sanchez is referring to are natural parts of our body’s defense system, which protect organs and tissues from various types of physical, biological, or chemical stress. In our joints, for instance, there exists a viscous fluid called the synovial fluid whose main purpose is to reduce friction between cartilage and the joint itself.
While vital, it limits the effectiveness of some injected arthritis medications as its thick, viscous nature reduces the drugs’ mobility, making it difficult to reach sites of injury and inflammation. To make their journey easier, Sanchez and his team turned to nanomotors that make the synovial fluid temporarily more liquid to help the medications reach their targets.
Making joint fluid more “liquid”
The approach involves two “troops” of injectable nanomotors composed of tiny, porous silica beads with enzymes attached to their surfaces.
first group is equipped with enzymes that break down the complex sugar molecules that make the joint fluid so thick and sticky. The second contains enzymes that react with urea, which is not natural to the joints but is added as a fuel before adding the nanomotors. Its purpose is to change the fluid’s pH as the urea is broken down by the motors into ammonia, which helps further lower the viscosity while also shutting down the first round of nanomotors.
“The idea with these different ‘troops’ is to reduce the viscosity of the synovial fluid but we want to do this in a controlled manner because we cannot have water in the joints,” said Noelia Ruiz-González, first author of the study. “The novelty of [our] approach is that the second troop is able to communicate with the first one in order to say, ‘Hey, I am increasing the pH’, and this pH stops the action of the first troop.”
Conveniently, the second type of enzymes stops working as soon as the urea is used up, thereby concluding all nanomotor activity.
In preliminary experiments, Sanchez and his team tested their tandem approach in plastic dishes. To visualize the mobility of arthritis drugs, such as growth factors or steroids, in the fluid, the team used fluorescent proteins which light up under a microscope and mimic the drugs’ size and bulkiness.
When injected in the sticky fluid, the fluorescent proteins formed a condensed lump that only dispersed after successively adding both types of enzyme-loaded nanoparticles.
Kinks to iron out
The journey from experiments in test tubes to being able to treat human patients is a long journey, and before any of this can happen, the nanomotors still need some fine-tuning and further testing. First and foremost, they need to be made compatible with biological systems.
“What we need to do is to change the particle. [We need] more bio-friendly nanoparticles, biodegradable, this cannot be silica,” said Sanchez. “Silica degrades after one month but you want to heal the patient in one day.”
The team say they are also working with clinicians who are looking to improve the effectiveness of regenerative therapies delivered via injection through the joint cavity. Their experience with different patients and knowledge will hopefully help the researchers adjust the formulation of their nanomotor cocktail.
“In the end, it’s the clinicians that are close to the disease,” said Sanchez. “We want to improve the efficiency of the treatment, that’s the point. We don’t develop drugs.”
Another concern is how the change in pH will affect joints in the short and long term. This is crucial as the pH of any bodily fluid, including the synovial fluid, is tightly regulated and any imbalance could have severe health implications, marking a potential red flag for the nanomotors. An improvement of the current design could be to have them operate at a more compatible physiological pH, for example.
While still in its preliminary stages, Sanchez and his team say there is potential to apply their nanomotors beyond just arthritis, combining them with different drugs to help boost the treatment of a wide range of diseases. For example, they’ve already begun tests in using the nanomotors to deliver drugs to treat bladder tumors in mice, reducing the tumor size by 90%.
Though not as advanced yet, it will be interesting to see how the tandem nanomotor approach to help treat arthritis evolves.
Reference: Samuel Sánchez, et al., Swarms of Enzyme-Powered Nanomotors Enhance the Diffusion of Macromolecules in Viscous Media, Small (2024). DOI: 10.1002/smll.202309387
Feature image credit: Towfiqu barbhuiya on Unsplash