Squid-inspired technology could replace needles in drugs and vaccines

Researchers have demonstrated a microjet system that uses squid-inspired jet propulsion to deliver drugs directly to tissue, rivaling the effectiveness of traditional needles.

In a recent study published in natureA research team led by scientists from the Massachusetts Institute of Technology and Novo Nordisk investigated a new needle-less microjet system for delivering drugs directly to the gastrointestinal tract.

Inspired by the jet propulsion systems of cephalopods, these devices are designed to efficiently deliver macromolecules such as insulin and ribonucleic acid (RNA) to the gastrointestinal tract via precise high-pressure jets. , potentially improving drug absorption and addressing challenges associated with traditional injections. -Based shipping method.

background

Macromolecular drug delivery relies on injection using needles, creating issues such as the need for medical training, the risk of needle-related injuries, and the difficulty of handling sharps. Recently, the development of ingestible devices provides a convenient alternative and may improve patient compliance.

However, current oral delivery devices struggle to effectively deliver large molecules such as proteins because they are susceptible to digestive degradation. Many oral systems also fail to achieve bioavailability levels comparable to subcutaneous injections. Additionally, although robotic and autonomous devices have shown some success in self-guided and needle-free drug delivery, these methods remain largely unexplored for gastrointestinal applications.

About research

In this study, inspired by the natural propulsion mechanisms observed in cephalopods, researchers develop a jet-based drug delivery approach that enhances the safe and effective delivery of large molecules in gastrointestinal tissues. The purpose was to They developed and tested a series of microjet devices (MiDe systems) designed to deliver drugs directly to the gastrointestinal tract.

Four device configurations were created. Two autonomous self-starting versions (MiDeRadAuto and MiDeAxAuto) and two versions compatible with endoscopic guidance (MiDeRadEndo and MiDeAxEndo). Furthermore, the orientation of each device was optimized for the specific gastrointestinal section. Radial models are designed to target tubular structures such as the small intestine, while axial models are suitable for larger areas of the stomach.

The device was first calibrated in a laboratory setting using the following method. in vitro and ex vivo I'll study. During these tests, the researchers varied nozzle diameter, input pressure, and jet angle to determine the optimal conditions for effective tissue penetration.

in vitro A study in porcine gastrointestinal tissue measured the depth and distribution of fluid delivery within tissue layers using computed tomography (CT) to visualize fluid spread. After these tests, the researchers fine-tuned the device's pressure and nozzle dimensions to produce high-pressure jets suitable for different gastrointestinal regions.

moreover, alive In trials, the MiDe device delivered therapeutic agents such as insulin, glucagon-like peptide 1 (GLP-1) analogs, and small interfering RNA (siRNA) to specific gastrointestinal sites in pigs and dogs. The researchers then collected regular blood samples to measure systemic bioavailability.

In addition, high-speed imaging was used to capture the jetting dynamics, allowing researchers to assess the stability and recoil of the device. Safety and accuracy tests were also conducted to confirm the suitability of the device for use in the gastrointestinal tract without causing adverse effects or damage to surrounding tissue.

result

The researchers demonstrated that the MiDe device significantly increases the delivery and bioavailability of macromolecules within the gastrointestinal tract. This device achieved high systemic absorption of insulin, GLP-1 analogs, and siRNA with performance comparable to subcutaneous injection.

Specifically, a radial endoscopic device (MiDeRadEndo) delivered GLP-1 with 67% bioavailability in the pig intestine, whereas an axial endoscopic device (MiDeAxEndo) delivered siRNA with 82% bioavailability in the stomach. bioavailability was achieved. The autonomous devices MiDeRadAuto and MiDeAxAuto demonstrated insulin bioavailability in pigs of 31% and 23%, respectively.

The results showed that bioavailability is influenced by factors such as jet angle, distance from tissue, and pressure level. A 40% decrease in volumetric delivery efficiency (VDE) was observed when the jet angle reached 45° with respect to the tissue.

Additionally, the self-orienting design of MiDeAxAuto allowed for stable positioning within the stomach, whereas MiDeRadAuto was unable to maintain a coaxial orientation within the intestine despite some variation due to animal movement. I was seen. Histological analysis also confirmed that the jet delivered the therapeutic agent deep into the target tissue layer without causing damage.

The radial device's dual nozzle design minimizes recoil and improves stability. Additionally, this device has demonstrated reliable safety and stability. alive and ex vivo Testing suggests that the MiDe system can safely and effectively deliver large molecules into the gastrointestinal tract.

conclusion

Overall, the results of this study demonstrate that the needle-free microjet-based MiDe system for drug delivery to the gastrointestinal tract can safely and effectively target specific gastrointestinal regions, while achieving similar biological efficacy to subcutaneous injections. Demonstrated achievement of availability level. These findings demonstrate that the MiDe platform can be used to advance oral drug delivery technology, making it possible to deliver macromolecular therapeutics directly to the gastrointestinal tract.