Cappelleri, associate professor of mechanical engineering at Purdue, calls the robots “magnetically aligned nanorods in alginate capsules” (MANiACs), and in the future they may be part of an advanced arsenal of drug delivery technologies at doctors’ disposal. A new study in open-access journal Frontiers in Robotics and AI is the first to investigate how such tiny robots might perform as drug delivery vehicles in neural tissue. The study finds that when controlled using a magnetic field, the tiny tumbling soft robots can move against fluid flow, climb slopes and move about neural tissues, such as the spinal cord, and deposit substances at precise locations.             

Diseases in the central nervous system can be difficult to treat. “Delivering drugs orally or intravenously, for example, to target cancers or neurologic diseases, may affect regions of the body and nervous system that are unrelated to the disease,” explained Lamar Mair of Weinberg Medical Physics, a medical device company based in the U.S. and an industrial partner on the study. “Targeted drug delivery may lead to improved efficacy and reduced side-effects due to lower off-target dosing.”

One way to achieve targeted dosing is to use tiny robots to deliver drugs to specific locations. While this technology is still in its infancy, researchers have developed various types of micro- or millirobots that could fulfill this ostensibly far-fetched goal. However, the major problem lies in controlling their activity as they travel through tissues in the body, and few researchers have put their robots to the challenge by seeing how they handle moving across real tissues.

Magnetic fields are a particularly promising way to control things inside the body, as they are not influenced by tissues and tend to be very safe. This is the power behind the MANiACs, which are tiny tumbling robots containing magnetic nanorods encased in a soft spherical shell. These properties should allow them to safely tumble through the body in response to a magnetic field applied externally, with the goal of drawing them to a target site for drug delivery.

The research team behind the current study wanted to test their MANiAC soft robots under conditions they may experience in the body. These include navigating the undulating and tortuous architecture of the nervous system, which includes flowing cerebral spinal fluid and steep slopes.

The researchers tested the ability of the MANiACs to climb slopes with increasing steepness and move against flowing liquid. They also obtained rat brains and mouse spinal cords to test the robots’ ability to move along the tissues and deposit a dye on their surfaces, as a substitute for a drug.

Under magnetic stimulation, the MANiACs successfully scaled slopes as steep as 45 degrees and moved upstream against a fluid flow that was similar to what they would encounter in the nervous system. The researchers were able to maneuver dye-loaded MANiACs around on the surface of rodent neural tissues with a fine degree of control, and successfully deposited the dye in specific locations. They even re-dosed several locations to increase the amount of ‘drug’ dosed to that region.

“The ability to go back and re-dose regions which received insufficient dose upon initial treatment is significant,” said Cappelleri. “These results are very preliminary and highly experimental, but we think we have demonstrated strong evidence that small, soft, capsule-based microrobots have potential for controlled local delivery in neural diseases.”

Source: David Cappelleri, dcappell@purdue.edu, 765-494-3719

ABSTRACT

Soft Capsule Magnetic Millirobots for Region-Specific Drug Delivery in the Central Nervous System

Lamar O. Mair, Georges Adam, Sagar Chowdhury, Aaron Davis, Dian R. Arifin, Fair M. Vassoler, Herbert H. Engelhard, Jinxing Li, Xinyao Tang, Irving N. Weinberg, Benjamin A. Evans, Jeff W.M. Bulte, David J. Cappelleri

Small soft robotic systems are being explored for myriad applications in medicine. Specifically, magnetically actuated microrobots capable of remote manipulation hold significant potential for the targeted delivery of therapeutics and biologicals. Much of previous efforts on microrobotics have been dedicated to locomotion in aqueous environments and hard surfaces. However, our human bodies are made of dense biological tissues, requiring researchers to develop new microrobotics that can locomote atop tissue surfaces. Tumbling microrobots are a sub-category of these devices capable of walking on surfaces guided by rotating magnetic fields. Using microrobots to deliver payloads to specific regions of sensitive tissues is a primary goal of medical microrobots. Central nervous system (CNS) tissues are a prime candidate given their delicate structure and highly region-specific function. Here we demonstrate surface walking of soft alginate capsules capable of moving on top of a rat cortex and mouse spinal cord ex vivo, demonstrating multi-location small molecule delivery to up to six different locations on each type of tissue with high spatial specificity. The softness of alginate gel prevents injuries that may arise from friction with CNS tissues during millirobot locomotion. Development of this technology may be useful in clinical and preclinical applications such as drug delivery, neural stimulation, and diagnostic imaging.