Researchers at the Massachusetts Institute of Technology (MIT), led by Giovanni Traverso, developed a microjet system inspired by the jet propulsion mechanisms of cephalopods such as squids and cuttlefish to deliver drugs directly to tissue without using needles. This microjet delivery system shows promise for the effective delivery of macromolecules like insulin and RNA to gastrointestinal tissues using high-pressure liquid jets, capturing the effectiveness of existing injection methods as a needle-free alternative.
Needle-based injections are effective but come with considerable challenges, including a risk of infections, difficulties in safely disposing of used equipment, patient discomfort, medical training requirements, and risk of needle injuries, making them not universally popular among patients. For decades, needle-based injections have been the main method for delivering large biological molecules such as insulin and vaccine components, but an aversion to needles is a significant reason why patients fail to keep up with their dosage. An aversion to needles leads one in six American adults to skip vaccinations, and this discomfort can also cause people to not adhere to treatment for chronic conditions.
Nature and The Economist reported on the research.
The new microjet system (MiDe) aims to increase patient adherence to treatment and improve drug absorption by overcoming the challenges associated with traditional needle-based drug applications. The microjet delivery systems mimic how cephalopods expel water and ink. Giovanni Traverso theorized that a system similar to how cephalopods propel ink and water at high pressure in all directions might be able to propel drugs with sufficient force to penetrate the soft tissues lining the digestive tract without needing the perfect angle required by needles.
The walls of the digestive system are extremely rich in blood vessels, making them an excellent location for deploying drugs. In the depths of the digestive tract, achieving the correct alignment for drug delivery is extremely challenging. For a syringe to properly deliver a drug, it must be nearly perpendicular to the target tissue. This requirement for alignment is true for injections into arms as well as for those into the lining of the gut.
The devices were designed in four different models suitable for autonomous and endoscopic guidance. The designs of the microjet delivery systems used two jetting approaches: axial jets for delivery into larger, globular organs such as the stomach and colon, and radial jets for smaller, tubular organs including the small intestine and esophagus. Radial models (MiDeRad) were optimized for tubular structures like the small intestine. An axial localization mechanism was implemented in the MiDe to align the jet for effective delivery in the stomach, a cavernous organ. The dual nozzle design reduced the backflow effect and increased stability.
Researchers optimized the microjet system (MiDe) to deliver drugs to gastrointestinal tissues. The devices were tested in the laboratory on various parameters such as nozzle diameter, pressure level, and jet angle. The aim of the force profile studies was to determine whether the devices produced sufficiently strong jets to deliver therapeutics. The microjet delivery systems highlight the system's efficiency and controllability.
In vivo tests successfully delivered therapeutic agents like insulin, GLP-1 analogs, and siRNA to the gastrointestinal regions of pigs and dogs, achieving bioavailability levels greater than 10%. For example, the delivery of insulin to the small intestine in pigs reached a bioavailability of 69% at a pressure of 9.4 bar. In dogs, the delivery of insulin to the stomach achieved a bioavailability of 90% at a pressure of 24.5 bar. The axial device (MiDeAxEndo) reached 82% bioavailability in the stomach with siRNA application. The microjet delivery devices achieved bioavailability levels of up to 90%, comparable to those achieved using injections under the skin.
The system's safety tests confirmed that it did not cause tissue damage and effectively delivered therapeutic agents to the target tissue. According to the research results, MiDe devices significantly increased the bioavailability of macromolecules in gastrointestinal tissue.
The technology has the potential to improve treatment compliance for chronic conditions that require frequent medication, addressing the significant issue of patient aversion to needles that often leads to missed dosages. The technology enables home-based treatments for a wider range of conditions. This technology could revolutionize drug and vaccine applications as an alternative to traditional methods, and the researchers expect that similar devices could one day be used to administer vaccines.
Although promising, the current study is limited to preclinical animal models, and future work should include broader in vivo testing with additional therapeutic agents and ex vivo testing using porcine and human organs to better understand biological variability. Further research is needed to establish safety and efficacy in humans, particularly regarding long-term use and potential side effects in gastrointestinal tissues. Future work will focus on manufacturing devices with optimal safety features that comply with regulatory guidelines. Researchers plan to explore biodegradable materials to increase the devices' environmental sustainability.
This article was written in collaboration with generative AI company Alchemiq