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In vitro applications in drug metabolism and cell encapsulation
Cell cultures of clinically relevant human cells were utilized in the development of in vitro models that better mimic in vivo physiological conditions. Specifically, liver models were developed to evaluate novel cell encapsulation and tissue engineering devices, and in the establishment of a system to study metabolism and toxicity of the anticancer agent paclitaxel. A novel viable cell encapsulation device was developed utilizing the hydrogel Pluronic® F127. Pluronic® F127 is a thermoreversible polymer that gels at body temperature and therefore has significant in vivo potential. The addition of membrane stabilizing agents (e.g., hydrocortisone) to the cell encapsulation device resulted in prolonged cell viability. Prior to this work, cytotoxicity was a major issue, which can now be circumvented using membrane-stabilizing agents. Exciting work also centered on oxygen supply in cell encapsulation devices, arguably the most pressing issue in realizing the commercial potential of tissue engineering. Novel processes were developed using perfluorocarbons (PFCs) to enhance oxygen availability to encapsulated cells. Specifically, encapsulated liver cells had enhanced viability, higher growth rates, and a suppression of anaerobic metabolism with inclusion of PFCs. These results have far reaching implications on all aspects of tissue engineering and are expected to make a significant impact in the broad community. Lastly, a novel in vitro system was established to assess paclitaxel toxicity and characterize metabolism. Specifically, HepG2 cells, a common liver model cell line, were transformed to metabolize paclitaxel for use in an in vitro model. The stability of paclitaxel was also assessed in vitro and it was found that significant changes were due to protein binding, pH, and unconditioned medium. The goal is to develop in vitro cell culture models that can supplement or replace animal studies, thereby reducing costs associated with assessing new chemical entities and obtaining information on adsorption, toxicity and metabolism in a high-throughput manner.
Khattak, Sarwat F, "In vitro applications in drug metabolism and cell encapsulation" (2006). Doctoral Dissertations Available from Proquest. AAI3215764.