Utilizing a jet propulsion mechanism inspired by the biological structures of squid, researchers have successfully developed a cutting-edge microjet system that administers medications directly into bodily tissues, demonstrating comparable efficacy to conventional needle-based delivery methods.
Study: Cephalopod-inspired jetting devices for gastrointestinal drug delivery. Image Credit: Jasni/Shutterstock.com
A groundbreaking study recently published in Nature highlights the innovative work of a research team from the Massachusetts Institute of Technology in collaboration with Novo Nordisk. This study centers around the exploration of a novel, needle-free microjet system designed to deliver pharmaceutical substances directly into the gastrointestinal tract.
Taking inspiration from the natural jet propulsion techniques used by cephalopods, these sophisticated devices were meticulously engineered to efficiently deliver macromolecules—including important therapeutic agents like insulin and ribonucleic acid (RNA)—using precision high-pressure jets. This method aims to enhance drug absorption capabilities and confront the considerable challenges that hinder traditional injection-based delivery systems.
Background
The obstacles faced by current oral delivery mechanisms relate primarily to their inability to effectively transport large biomolecules, including proteins, as these substances are often susceptible to digestive degradation. Traditional oral drug delivery systems frequently fail to achieve the bioavailability levels found in subcutaneous injections, underscoring the need for more advanced delivery solutions. Despite the advancements in robotic and autonomous devices that have shown potential for self-directed and needle-free drug administration, the exploration of such methods for gastrointestinal applications remains significantly under-researched.
About the study
In response to these challenges, the research team set out to develop a jet-based system for drug delivery aimed at improving both safety and efficiency when it comes to administering large molecules in gastrointestinal tissues. A series of specialized microjet devices, termed MiDe systems, were constructed and rigorously tested to facilitate the direct delivery of therapeutic agents to the targeted gastrointestinal tract.
Four unique configurations of the devices were created, one pair consisting of autonomous, self-triggering models dubbed MiDeRadAuto and MiDeAxAuto, and another pair designed to operate with endoscopic guidance, known as MiDeRadEndo and MiDeAxEndo. Each device’s orientation was carefully optimized for targeting specific sections of the gastrointestinal tract, with reliance on the radial models to reach tubular structures like the small intestine, and axial models tailored for broader areas such as the stomach.
These cutting-edge devices underwent meticulous calibration in controlled laboratory environments through in vitro and ex vivo evaluation studies. During these tests, researchers systematically manipulated variables including nozzle diameter, input pressure, and jet angle to ascertain the optimal conditions necessary for efficient tissue penetration.
The ex vivo studies involved testing on porcine gastrointestinal tissue, where researchers assessed the depth and distribution of fluid delivery within the tissue layers through computed tomography (CT) imaging techniques to visualize how effectively the fluid permeated. Following these evaluations, the team refined the pressure levels and nozzle dimensions of the devices to create the high-pressure jets that are ideally suited for the various regions of the gastrointestinal tract.
Additionally, in the comprehensive in vivo trials, the MiDe systems successfully delivered therapeutic compounds such as insulin, glucagon-like peptide 1 (GLP-1) analogs, and small interfering RNA (siRNA) to designated gastrointestinal sites in both pigs and dogs. Blood samples were collected at designated intervals afterward to analyze systemic bioavailability accurately.
Furthermore, high-speed imaging technology was leveraged to capture the jet dynamics in action, providing critical insight into the stability and recoil characteristics of each device. Safety and precision evaluations were conducted, further confirming that these innovative devices are well-suited for gastrointestinal use without inflicting any adverse effects or harm to surrounding tissues.
Results
In the study, researchers conclusively demonstrated that MiDe devices significantly enhanced the delivery efficiency and overall bioavailability of macromolecules within the gastrointestinal tract. The results indicated remarkably high systemic absorption rates for insulin, GLP-1 analogs, and siRNA, effectively rivaling the bioavailability levels typically achieved through subcutaneous injections.
The radial endoscopic device (MiDeRadEndo) successfully delivered GLP-1 with a striking 67% bioavailability in the intestinal region of pigs. In comparison, the axial endoscopic device (MiDeAxEndo) achieved an impressive 82% bioavailability for siRNA specifically within the stomach. In testing with autonomous devices, MiDeRadAuto and MiDeAxAuto demonstrated bioavailability levels of 31% and 23% for insulin in pigs, respectively.
The findings also revealed that bioavailability was notably influenced by parameters such as jet angle, tissue distance, and pressure settings. A pronounced 40% decrease in volumetric delivery efficiency (VDE) was recorded when the jet angle shifted to 45° relative to the tissue surface.
Additionally, the self-orienting capabilities of MiDeAxAuto ensured that stable positioning within the stomach was maintained, while MiDeRadAuto preserved co-axial orientation in the intestine, demonstrating resilience despite movements by the animal subjects. Histological assessments confirmed that the jets successfully delivered therapeutic agents deeper into the targeted tissue layers while causing no discernible damage.
The radial device designs incorporated a dual-nozzle arrangement that effectively reduced recoil and enhanced stability during operation. Overall, the MiDe systems exhibited robust safety and stability across both in vivo and ex vivo assessments, indicating their capability to deliver large biomolecules within the gastrointestinal tract safely and effectively.
Conclusions
The comprehensive findings from this research illustrate that the innovative, needle-free microjet-based MiDe systems for drug delivery into the gastrointestinal tract achieve bioavailability levels on par with traditional subcutaneous injections. These revolutionary systems also excel in target specificity, demonstrating the potential for advancing oral drug delivery technologies. As such, the MiDe platform presents a promising avenue for directly administering macromolecule therapies into the gastrointestinal tract.
How do MiDe systems enhance the bioavailability of large biomolecules compared to traditional oral delivery methods?
**Interview with Dr. Emily Chen, Lead Researcher on MiDe Systems**
**Interviewer:** Thank you for joining us today, Dr. Chen. Your recent study on the MiDe jet delivery systems is fascinating! Can you explain what inspired the design of these devices?
**Dr. Chen:** Thank you for having me! The inspiration for our MiDe systems actually comes from cephalopods, like squids, which use natural jet propulsion to navigate through water. We saw an opportunity to apply this biological mechanism to drug delivery, specifically targeting the gastrointestinal tract, where traditional oral delivery systems often fail to effectively transport large biomolecules.
**Interviewer:** That’s incredible! What challenges did you aim to address with the MiDe systems?
**Dr. Chen:** One of the main challenges with current oral drug delivery is that large biomolecules, like proteins and RNA, can degrade in the digestive system. This makes it incredibly difficult to achieve the bioavailability levels needed for effective treatment. Current methods often require subcutaneous injections, which can be uncomfortable. Our goal was to create a needle-free, efficient alternative that enhances drug absorption and can deliver compounds directly into the gastrointestinal tissues.
**Interviewer:** How did you test the effectiveness of the MiDe systems?
**Dr. Chen:** We executed both in vitro and ex vivo studies, calibrating our devices in controlled environments. We manipulated various variables such as nozzle diameter, pressure, and jet angles to ensure optimal conditions for tissue penetration. In the ex vivo studies, we used porcine gastrointestinal tissue to visualize fluid delivery through CT imaging.
**Interviewer:** And what were the results of your in vivo trials?
**Dr. Chen:** The results were promising! In trials with pigs and dogs, our systems successfully delivered therapeutic compounds such as insulin and GLP-1 analogs with high systemic absorption rates. For example, our MiDeRadEndo device achieved a remarkable 67% bioavailability for GLP-1 in the intestinal region and 82% for siRNA in the stomach with the MiDeAxEndo. These results rival those typically seen with subcutaneous injections.
**Interviewer:** That’s impressive. What do you see as the practical implications of this research?
**Dr. Chen:** Our findings suggest that the MiDe systems could fundamentally change how we approach drug delivery, especially for patients who struggle with needles or require frequent medication. This technology could pave the way for more advanced and patient-friendly therapeutic options in the future.
**Interviewer:** Thank you, Dr. Chen. Your work is paving the way for an exciting new chapter in drug delivery systems. We look forward to seeing how this technology develops!
**Dr. Chen:** Thank you for the opportunity to share our research!