The aim of this study is to prepare and characterize polymer drug-conjugate delivery system loaded with doxorubicin and melphalan for successful passive or active targeting of these anti-cancer agents to the tumor environment by the enhanced permeability and retention effect and targeted tumor drug delivery. The polymers will be investigated in in vitro cell cultures of various cancers.
The preliminary study in this research focuses on preparation and characterization of polymer-drug conjugates. Doxorubicin and melphalan constitute the model chemotherapeutic agents for conjugation because doxorubicin exhibits maximum absorbance at 490nm where as melphalan exhibits maximum absorbance at 260nm. This difference in absorbance allowed differential characterization of both drugs when conjugated to the polymers. In addition, the mechanisms of chemotherapeutic actions of doxorubicin and melphalan are different.
In-vitro studies using polymer drug-conjugate were also conducted to support the concept that tumor toxicity would be enhanced compared to equal concentrations of individual anti-cancer agents. The rationale is due to these reasons: (1) macromolecules such as polymer-drug conjugates will be concentrated in the tumor environment by enhanced permeability and retention effect, and (2) two different anti-cancer agents that have different cytotoxic activities delivered simultaneously to tumor cells should be more effective than individual drugs.
Successful completion of the above mentioned study confirm that the polymer-drug delivery system can be used for more efficient multi drug cancer therapy.
|Commitee:||Epstein, Slava, Gatley, John S.|
|School Location:||United States -- Massachusetts|
|Source:||MAI 50/01M, Masters Abstracts International|
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