主题：Photo-triggered polymer-drug conjugates for pain medicines

报告人：张炜 

时间：2024年7月17日（周三）10:00-12：00

地点：化学楼A楼518会议室

邀请人：王大力 副教授

个人简介

 Dr. Wei Zhang joined the Department of Pharmaceutical Science at the University of Pittsburgh as an Assistant Professor in 2023. Prior to Pitt, he was an Assistant Professor in Anesthesia at Harvard Medical School.

He received his BS degree in Chemistry from Peking University in 2011, and worked on liquid crystal polymers for light-emitting diodes in the lab of Prof. Qifeng Zhou. He received his PhD in Polymer Science in 2016 from the University of Akron with Prof. Stephen ZD Cheng’s (NAE), and worked on synthesis and supramolecular structures of precise macromolecules based on molecular nanoparticles and polymer-nanoparticle conjugates. Then, he did postdoc training at Harvard Medical School, Boston Children’s Hospital with Profs. Daniel Kohane & Robert Langer, where he worked on various applications of biomedical materials, including photo-controlled drug delivery for local anesthesia, non-invasive local drug delivery system for otitis media, polymeric tissue adhesives and drug-eluting contact lens. He is author of 50 publications and 4 patents (1 licensed to a company), and he is a recipient of the NIH Pathway to Independence Award.

报告摘要

Polymers can offer novel solutions to biomedical challenges. This talk will present examples of stimuli-responsive polymers for drug delivery. The first one is on-demand local anesthesia by a photo-triggerable polymeric prodrug. A local anesthetic release system that would only take effect when and where needed is highly desirable. Here, we design and synthesize a macromolecular prodrug (P407-CM-T) in which the local anesthetic tetracaine (T) is attached to the polymer poloxamer 407 (P407) via a photo-cleavable coumarin linkage (CM). P407-CM-T solution is an injectable liquid at room temperature and gels near body temperature. The macromolecular prodrug has no anesthetic effect itself unless irradiated with a low-power blue light emitting diode (LED), resulting in local anesthesia. By adjusting the intensity and duration of irradiation, the anesthetic effect can be modulated. Local anesthesia can be repeatedly triggered. Another example is a photo-triggered naloxone delivery. Naloxone is an opioid antagonist for treatment of opioid overdose. However, prolonged constant release of naloxone could interfere with normal usage of opioids, such as in acute perioperative use. Here, naloxone was attached to the polymer poly(lactic-co-glycolic acid) via a coumarin linkage and formulated as injectable nanoparticles. In the absence of irradiation, the formulation would not interfere with opioids. Upon irradiation with blue light, the nanoparticles released free naloxone, reversing the effect of morphine in mice. Such triggered events could be performed days and weeks after the initial administration of the nanoparticles and could be performed repeatedly.