Congratulations to Ph.D. student Xize Gao & Jiacong Li et.al. published an article in “Science Advances“
Inspired by the expansion of the diodon holocanthus, the team of Professor Mingjun Zhang from Tsinghua University School of Medicine and Associate Professor Jing Xu from the Department of Mechanics have jointly developed a painless and biodegradable drug-delivery robot that uses intestinal peristalsis to drive microneedles into the intestinal wall. Animal experiments on small Parmesan pigs showed that the robot delivered insulin with a bioavailability of 23.6% and was able to pass through the digestive tract of the small pigs without causing intestinal obstruction. Histological analysis of the intestine showed rapid recovery of the microneedle-entrapped portion of the intestinal wall with limited inflammatory response. The work was published in Science Advances under the title “Pain-free oral delivery of biologic drugs using intestinal peristalsis-actuated microneedle robots“.
Fig. 1 Intestinal peristalsis-driven spiny dolphin-inspired microneedle robot for oral delivery of biopharmaceuticals
In order to design the size of the robot to ensure that the microneedle could puncture the intestinal wall when subjected to small intestinal compression, the authors performed intestinal manometry and microneedle penetration assessment on Parma mini pigs. The intestinal peristaltic pressure exerted by different robot sizes was measured by a capsule-shaped manometric sensor and the minimum size of the microneedle robot was determined by comparing it with the force required to puncture the small intestinal tissue with the microneedle. The mechanical analysis of the swelling process of the microneedle robot was then used to design the size of the microneedle robot before swelling, the modulus of elasticity of the stretchable membrane, and the filling ratio of the hydrogel particles. So that it can be placed into an enteric capsule, but also reach enough size after swelling to generate enough peristaltic pressure, while maintaining enough stiffness to support the drug-carrying microneedles to puncture into the intestinal wall (Fig. 2). Moreover, the authors designed the drug-carrying microneedles into a double-layer barbed structure, which can ensure that the drug-carrying layer can be broken in the intestinal wall during intestinal diastole to achieve continuous drug delivery (Figure 3).
Fig. 2 Intestinal manometry and microneedle puncture experiments
Fig. 3 Barbed microneedle design and experiment
Finally, experiments performed on Parma miniature pigs showed that insulin delivery using the barbed microneedle robot proposed in this study achieved 23.6% bioavailability, which is 37.7 times higher than that of direct oral insulin administration. Also, the comparison with the delivery effect of the barbless microneedle robot illustrates the contribution of the barbed structure. Moreover, consecutive radiographs taken over a week showed that all five capsules containing barium sulfate delivered to the esophagus of minipigs passed through the pig’s digestive tract smoothly and did not lead to obvious abnormalities, such as intestinal obstruction and changes in eating habits. The above experiments verified the effectiveness and safety of the microneedle robot as an oral delivery platform for biological drugs. (Figure 4)
Fig. 4 Validation of effectiveness and safety of microneedle robots
The authors conclude by showing that the intestinal peristalsis-driven microneedle robot proposed in this study provides a promising platform for the oral delivery of biologic drugs, with the potential to improve therapeutic comfort in several areas. However, as the frequency and intensity of intestinal peristalsis varies considerably between individuals, future clinical studies may need to consider how to make it work across a wider range of individual differences. Professor Mingjun Zhang of Tsinghua University School of Medicine and Associate Professor Jing Xu of the Department of Mechanical Engineering were the co-corresponding authors of the paper, while doctoral student Xize Gao of the School of Medicine and doctoral student Jiacong Li of the Department of Mechanical Engineering were the co-first authors. This study was funded by the National Natural Science Foundation of China and other programmes.
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