Faculty + Staff

Dr. Rebecca L. Carrier

Assistant Professor Ph.D. (Chemical Engineering) Massachusetts Institute of Technology, 2000 Contact: Phone: 617.373.7126 Email: r.carrier@neu.edu Website: http://www.coe.neu.edu/~rebecca

Research Focus/Background

The goal of our research program is to increase understanding of fundamental transport phenomena in the drug delivery environment. These phenomena are studied via development of theoretical and tissue-engineered cell culture models of drug delivery systems. The current common approach to development of a drug delivery device in the pharmaceutical and biotechnology industries involves device design followed by testing in animals and/or humans. While the end result (i.e. typically the profile of blood plasma drug concentration over time) of these studies indicates whether or not the drug delivery system works, the reason for system failure and the robustness of the system is often not well characterized or understood. A quantitative understanding of the influence of the properties of the system being considered (therapeutic agent, drug delivery vehicle, biological environment) on the desired transport of the therapeutic agent are essential to the rational evaluation and design of drug delivery systems. Computational models that incorporate the key physical and chemical properties of the therapeutic agent, drug delivery vehicle, and biological environment, in concert with appropriate experiments for model validations and physical parameter measurement, will allow greater understanding of what drug delivery systems will work for a given therapeutic agent and delivery site, and how. Models are in the form of kinetic equations and mass, energy, and momentum balances. Model parameters relate physical and chemical properties of the therapeutic agent, drug delivery vehicle, and biological environment to the resulting transport of therapeutic agent. Model parameters represent and thus provide insight into phenomena at the molecular scale that influence the delivery of therapeutic agents to a biological environment of interest (GI tract, eye, muscle, lung, skin, etc.). Specific drug delivery systems being modeled include controlled co-delivery of a drug and complexing agent to the GI tract and non-viral vector gene delivery to cells.

In parallel with theoretical model development, tissue engineered models of the drug delivery environment are being developed to aid in rational formulation design in the pharmaceutical and biotechnology industries. Current in vitro analyses commonly used for testing drug delivery devices (e.g. dissolution tests, Caco-2 cells) are difficult to translate to expected in vivo results. This is related to lack of biological response in the case of common dissolution tests and to known differences between in vitro cell lines and the in vivo counterpart (expression of carrier proteins, permeability of intracellular junctions, enzymatic activity, mucous content, morphology) in the case of cell-based assays. However, in vivo testing often does not provide insight into the mechanism of failure of a device as it typically involves the black box approach of dosing and measuring the resulting drug blood plasma profile. The ability to study drug delivery devices in vitro would be greatly enhanced by the availability of in vitro tissue analogues that closely mimic the in vivo drug delivery environment. We are developing such devices, with a research focus on understanding how the chemical and physical properties of the biomaterial substrate used to culture the tissue (micro- and nano-architecture, chemical composition, surface functionality, etc.) influence the phenotype (protein expression, morphology, intracellular junction formation) of the cells comprising the tissue. Initially, efforts will focus on using tissue engineering concepts to create a model of intestinal tissue (improvement on Caco-2). This research is intended to expand to development of tissue engineering models of different drug delivery sites (e.g. ocular, pulmonary, transdermal, intramuscular, etc.).

Research Areas:

• Modeling of Drug Delivery
• Enhancement of Drug Solubility and Absorption
• Molecular Modeling of Mucosa-Delivery System Interactions
• Tissue Engineering of Intestine
• Modeling Cellular Gene Delivery Processess

Publications:

"Effects of oxygen on engineered cardiac muscle." R.L. Carrier, M. Rupnick, R. Langer, F. J. Schoen, L. E. Freed, G. Vunjak-Novakovic, Biotechnol. and Bioeng, 78(6), 616-624 (2002).

"Perfusion improves architecture of engineered cardiac muscle." R. L. Carrier, M. Rupnick, R. Langer, F. J. Schoen, L. E. Freed, G. Vunjak-Novakovic, Tissue Eng, 8(2), 175-188 (2002).

"Hydrolysis in pharmaceutical formulations." K. D. Waterman, R. C. Adami, K. M. Alsante, A. S. Antipas, D. R. Arenson, R. Carrier, J. Hong, M. S. Landis, F. Lombardo, J. C. Shah, E. Shalaev, S. W. Smith, H. Wang, Pharm Dev Technol, 7(2), 113-146 (2002).

"Cardiac tissue engineering: cell seeding, cultivation parameters, and tissue construct characterization." R. L. Carrier, M. Papadaki, M. Rupnick, F. J. Schoen, N. Bursac, R. Langer, L. E. Freed, G. Vunjak-Novakovic, Biotechnol Bioeng, 64, 580-589 (1999).

"Cardiac muscle tissue engineering: towards an in vitro model for electrophysiological studies." N. Bursac, M. Papadaki, R. J. Cohen, F. J. Schoen, S. R. Eisenberg, R. L. Carrier, G. Vunjak-Novakovic, L. E. Freed, Am J Physiol, 277(2, Pt 2), H433-H444 (1999).