Microbots in Drug Delivery

 In recent times, the evaluation of nanoparticles and nanotubes in safe and specific drug delivery has been intense in the medical field, however, conventionally these nanoparticles are made up of carbon or gold, both of which are toxic to the human system. Nanoparticle drug delivery may seem to be a familiar term now because the covid vaccines developed by Pfizer and Moderna are packaged in nanoparticles, and the entire scenario has been a talked about topic. The manifold increase in efficacy of a drug when specifically administered in targeted cells is the driving point for researchers to bring out more possible ways for specific drug delivery and that is where the idea of fiction-like heroic microbots delivering drugs has emerged. Moving forward to the very intimidating recent advancements in targeted drug delivery -

 

As published on September 22, 2022, in Nature Materials paper, a study by Zhang, F., Zhuang, J., Li, Z. et al. at the University of California San Diego has brought to light the use of a conglomerate of naturally occurring microalgae and antibiotic encumbered polymeric nanoparticle encapsulated with the membrane of the phagocytic cell - neutrophil, thus bringing to existence hybrid microbots for effectual dissemination of drugs in vivo. This cognition is at the proof-of-concept stage, the team has demonstrated the apperception by treating the mice which are experimentally infected by Pseudomonas aeruginosa, which is the causative agent of a fatal form of pneumonia that hurries patients into the Intensive Care Unit seeking Mechanical Ventilation. As the results turned out on inoculating the microbots into the lungs of the infected mice, the microbots administered to infected mice showed clearance of symptoms within a week and survived in health past thirty days, however, the non-treated ones succumbed to death in the course of three days. This process shows better efficacy than Intravenous Therapy (IV) of antibiotics which involves dissipation of the drug throughout the bloodstream and also no substance, toxic or not, is left behind, all of it is sequestered by the body’s potent immune system.

 

In another proof-of-concept study by Chen Xin, Dongdong Jin et.al that was first published in American Chemical Society-Nano on 19 October 2021, it was perceived that they were able to prepare shape morphing microbots- a classical demonstration of biomimetic robots, that can precisely deliver chemotherapeutic drugs to cancer cells without causing any adverse side effects which are normally observed in conventional methods. For example, a fish-shaped microbot that is 4D printed using a pH-responsive hydrogel and immersed in a suspension having iron oxide nanoparticles has an adjustable ‘mouth’ that can open and close in response to changes in pH. This ‘fish’ can also be steered using magnets through simulated blood vessels to reach cancer cells in a petri dish. On lowering the pH of the surrounding medium, the fish opens its mouth and releases a drug that can kill cancer cells nearby.  Although the experiments with this biomimetic robot have been successful and very promising in vitro, for in vivo experiments the microbots need to be even smaller in size in order to navigate actual blood vessels and a suitable imaging method needs to be recognized in order to track their precise movements in the body.

 

 In addition to this, scientists at the Massachusetts Institute of Technology have invented a robotic pill that can successfully cross through the mucus barrier of the gastrointestinal tract and deliver drugs that are usually very difficult to administer orally as a method of treatment because the mucus layer that lines the gastrointestinal tract creates a steric hindrance making it difficult for the pill to pass through This “RoboCap” capsule carries its drug payload at one end and has its tunnelling features at the other end. On taking orally, this capsule travels to the alimentary canal where its gelatin cover dissolves when it encounters a specific pH. This change in pH also triggers a tiny motor inside the RoboCap to start spinning which helps the capsule to pass through the mucus barrier and displace it. It also has small studs that ‘brush’ the mucus away. Once the drug is dispersed locally, the capsule passes through the digestive tract on its own, without causing any inflammation or irritation. It has been experimentally observed that we can deliver drugs like vancomycin and insulin easily in this way. This revolutionary research was led by Shriya S. Srinivasan et.al and published on 28 September 2022.

 

These tantalising recent research works give us a taste of the advancements in biotechnological fields and related interdisciplinary fields imploring the boundaries in the fields of target drug delivery which increase overall efficacy, and minimal usage in a non-invasive highly penetrative drug delivery method. These methods need more dedicated research to make these processes validated to scale up in larger animals and eventually in humans. These researches are stepping stones for the transformation of the death sentence giving diseases like cancer into livable chronic diseases with a high quality of life, as these conceptual approaches can potentially eliminate the concerning side effects which come intermingled with life-saving drugs.

Authors : Sruty Dey, Heeya Gupta 

 

 

 

REFERENCES:

1.Zhang, F., Zhuang, J., Li, Z., Gong, H., de Ávila, B. E., Duan, Y., Zhang, Q., Zhou, J., Yin, L., Karshalev, E., Gao, W., Nizet, V., Fang, R. H., Zhang, L., & Wang, J. (2022). Nanoparticle-modified microrobots for in vivo antibiotic delivery to treat acute bacterial pneumonia. Nature materials, 10.1038/s41563-022-01360-9. Advance online publication. https://doi.org/10.1038/s41563-022-01360-9

2.Environmentally Adaptive Shape-Morphing Microrobots for Localized Cancer Cell Treatment

Chen Xin, Dongdong Jin, Yanlei Hu, Liang Yang, Rui Li, Li Wang, Zhongguo Ren, Dawei Wang, Shengyun Ji, Kai Hu, Deng Pan, Hao Wu, Wulin Zhu, Zuojun Shen, Yucai Wang, Jiawen Li, Li Zhang, Dong Wu, and Jiaru Chu

ACS Nano 2021 15 (11), 18048-18059

DOI: 10.1021/acsnano.1c06651

3.Srinivasan, S. S., Alshareef, A., Hwang, A. V., Kang, Z., Kuosmanen, J., Ishida, K., Jenkins, J., Liu, S., Madani, W., Lennerz, J., Hayward, A., Morimoto, J., Fitzgerald, N., Langer, R., & Traverso, G. (2022). RoboCap: Robotic mucus-clearing capsule for enhanced drug delivery in the gastrointestinal tract. Science robotics, 7(70), eabp9066. https://doi.org/10.1126/scirobotics.abp9066

4.Sheikhpour, M., Barani, L., & Kasaeian, A. (2017). Biomimetics in drug delivery systems: A critical review. Journal of controlled release : official journal of the Controlled Release Society, 253, 97–109. https://doi.org/10.1016/j.jconrel.2017.03.026

5.Xiao, Q., Li, X., Li, Y., Wu, Z., Xu, C., Chen, Z., & He, W. (2021). Biological drug and drug delivery-mediated immunotherapy. Acta pharmaceutica Sinica. B, 11(4), 941–960. https://doi.org/10.1016/j.apsb.2020.12.018

6.Manzari, M. T., Shamay, Y., Kiguchi, H., Rosen, N., Scaltriti, M., & Heller, D. A. (2021). Targeted drug delivery strategies for precision medicines. Nature reviews. Materials, 6(4), 351–370. https://doi.org/10.1038/s41578-020-00269-6