W. Mark Saltzman, Chemical Engineering

Polymers for the controlled release of drugs, proteins, and DNA

We have developed polymer implants that permit the controlled release of small and large molecules, including proteins and nucleic acids, at constant rates for periods of weeks to months. Our research is aimed at understanding the mechanisms of drug release from polymer matrices, understanding the fate of compounds released from implants into tissues, and designing implants for the treatment and prevention of human disease. Controlled release polymers may be particularly useful in the treatment of serious brain diseases, including Alzheimer's disease and brain tumors.

We are also developing polymers for releasing antibodies and vaccine proteins into the mucus secretions to provide protection against the transmission of disease. These devices may be effective for blocking the transmission of sexually transmitted diseases such as AIDS. We believe that this work will lead to new, inexpensive methods for controlling the spread of sexually transmitted diseases and is partially supported by the National Science Foundation/Whitaker Foundation joint program on Cost- Reducing Health Care Technologies.

Three dimensional cell cultures that mimic tissue Biological tissues contain many components--cells, extracellular matrix proteins and sugars, diffusable signalling molecules, and water--arranged in a three-dimensional configuration that is essential for tissue function. By assembling each of these components into three-dimensional cell culture, we can reproduce some of the features of tissues and study them in a controlled way. We are using these three-dimensional cell cultures to understand how cells grow, move, and function within tissues and to develop new methods for manipulating cell behavior in the body. Presently, we are using these methods to study the growth and function of neural tissues, and the ability of white blood cells to migrate during infection and immune recognition.

Mechanisms of drug transport in the body and advanced drug design

When biologically active molecules are released into the body, they must be transported to their site of action. In conjunction with the controlled release projects described above, we are measuring rates of transport of compounds in different biological systems. We are particularly interested in the transport of antibodies or other large molecules is tissues. In our approach, we combine in vitro measurements--using fluorescence light microscopy--with selected experiments in animals. These studies are providing insight into the mechanisms of drug transport and elimination at selected tissue sites.

Based on studies like these, we are learning the factors that control drug transport and elimination and, based on this information, designing new drug compounds that will have enhanced activities. For example, since we learned that high molecular weight molecules are selectively retained within certain brain structures, we are designing and building polymeric drug analogs that will target and enhance the treat ment of malignant brain tumors.