(442g) Using 3-D Tissue Model in High-Throughput Screening: Key to Improve Drug Discovery
AIChE Annual Meeting
2006
2006 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Engineering Treatment and Analysis of Diseases Poster Session
Wednesday, November 15, 2006 - 3:15pm to 5:45pm
High-throughput screening (HTS) has been widely used in the current ?fail early, fail fast? pharmaceutical industries during the target identification and hit/lead identification. However, the ease of these steps using HTS leads to a large number of poorly qualified leads before expensive animal tests, which are the inreplacable step difficult to be speeded up. Obtaining more in-vivo biological information in HTS will help to make a better decision to reduce the number of leads into animal experiments and thus is one of the most efficient ways to improve drug discovery process. A high-throughput, real-time, bioactivity assay based on the three-dimensional (3-D) culture of green fluorescent protein (GFP)-expressing mammalian cells has been reported in our lab. Toxicity of embryotoxic reference chemicals and anti-cancer drugs was measured in our 3-D multicellular model and the predicted toxicity was compared to that from mololayer culture. It showed that our 3-D system was a more realistic pharmacotoxicological test system than monolayer culture. With this 3-D system, acquired tissue resistance in the treatment of bulky tumor tissue was revealed in a high-through manner. As a bridge over the gaps between monolayer cell culture and animal models, our system can be used to improve drug discovery process when being applied in toxicity and efficacy testing before animal tests.