(6z) On-Demand Therapeutics: From Externally-Triggerable Drug Delivery Systems to Bioelectronics

Current treatment of pain heavily relies on opioids, with significant side effects such as addiction, clouded sensorium, tolerance and respiratory depression. Conventional local anesthetics may be effective with limited side effects, yet their duration of analgesia after a single injection is often insufficient for many pain states, including acute pain. As a result, pain management is in need of an effective and safe pain relief therapeutic system with limited side effects. My goal in research is to bridge this gap and develop platforms that may provide the opportunity for patients to have a better quality of life.

Externally-triggerable drug delivery systems provide a promising strategy for the treatment of pain. Such systems enable personalize and flexible control on the release of therapeutics, at the desired dosage, timing, and location according to the changing pain states of the patient. During my Ph.D. studies, near infrared light-activated pain relief systems using light-triggerable liposomes loaded with local anesthetics were developed. The incorporation of mechanisms such as photosensitization and photothermal effects made light-triggerable pain relief achievable in vivo at the sciatic nerve. It was shown that by changing the activating parameters of the near infrared light (e.g. the intensity and duration of activation), the dosage of drug release (and thus the degree of nerve block) was adjustable for multiple events within a single injection. Such repeatable and adjustable drug delivery systems demonstrated the promising potential of on-demand pain relief. Furthermore, the activating trigger was not limited to near infrared light. Ultrasound penetrated more effectively through tissue than near infrared light, and was used as the energy source of an ultrasound-triggerable pain relief system that demonstrated strong effectiveness in vivo. In summary, on-demand pain relief systems can be versatile and provides an effective strategy for pain management.

Pain management may benefit not only from an effective therapeutic system, but also from a powerful diagnostic system to better determine the degree of pain for clinical evaluation. Bioelectronics that can monitor pain responses, such as changes in heart rate, respiration rate, temperature and blood pressure, may provide a quantitative measurement of pain. In my postdoctoral research, I am developing bioelectronic systems for the monitoring of critical tissue properties, such as brain oxygenation and hydration. I am also performing clinical measurements of vital signs on neonatal patients. My training in translational research and bioelectronics development equips me with the toolsets to contribute to pain management.

I have a strong interest in the development of novel diagnostic and drug delivery systems for pain treatment. To merge such interest with my current training in translational research, I aim to invent and develop systems that benefit those who suffer from pain.

Fellowships

TL1 Postdoctoral Training Award, National Institutes of Health (NIH), 2017-2019

Chyn Duog Shiah Memorial Fellowship, MIT Office of the Dean for Graduate Education, 2014-2015

Selected Publications

1. Enhanced triggering of local anesthetic particles by photosensitization and photothermal effect using a common wavelength

Rwei A, Wang BY, Ji T, Zhan C, Kohane DS, Nano Letters 2017; 17 (11): 7138–7145

2. Ultrasound-triggered local anaesthesia

Rwei A, Paris JL, Wang B, Wang W, Axon CD, Vallet-Regí M, Langer R, Kohane DS,

Nature Biomedical Engineering 2017; 1, 644–653

3. Multiply repeatable and adjustable on-demand phototriggered local anesthesia

Rwei A, Zhan C, Wang B, Kohane DS, Journal of Controlled Release 2017; 251: 68-74

4. Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes

Rwei A, Lee JJ, Zhan C, Liu Q, Ok M, Shankarappa SA, Langer R, Kohane DS, PNAS 2015; 112 (51): 15719-15724

5. Photoresponsive nanoparticles for drug delivery

Rwei A, Wang W, Kohane DS, Nano Today 2015; 10(4): 451–467.

Teaching Interests:

Education and mentorship have been important aspects of my career. During my engineering training, my mentors have led me to the world of science, engineering and research, equipping me with enthusiasm and passing on their profound knowledge. I am grateful to my mentors, and I aim to pass down this experience to my students. During my TA experience in graduate school, I have found that patience, enthusiasm, and empathy are some of the most important aspects in teaching. As a mentor, seeing the students understanding a new concept, solving a new problem, and demonstrating confidence and enthusiasm in the subject, is the most rewarding experience. I received the “John Wulff Award for Excellence in Teaching an Undergraduate Subject” award from the MIT Department of Material Science when I graduated from MIT, as well as the historically highest TA evaluation score from the students’ end-of-semester evaluations of the subject. My goal and interest in mentorship is to equip our students with enthusiasm in engineering and science, and guide them to understand the importance of the subject and knowledge they are trained upon. My hope is that together, we can make this world a better place through the advancement of engineering and science.