Date on Master's Thesis/Doctoral Dissertation
Frieboes, Hermann Bueno
Drug delivery devices; Nanoparticles--Therapeutic use; Cancer--Treatment
Currently, the clinical strategy to treat cancer consists of a combination of surgery, radiotherapy, and chemotherapy on the basis of clinical and molecular staging. Nanotechnology applied to biomedical sciences has paved the way for the development of novel strategies for early detection and more efficient treatment of diseases. Abraxane and Doxil are approved formulations that utilize nanoparticles carrying the drugs paclitaxel and doxorubicin, respectively; however, tumors are not completely eradicated in some patients. It is well known that inefficient vascularization may prevent optimal transport of oxygen, nutrients, and therapeutics to cells in solid tumors. In order to quantitatively evaluate therapy with Abraxane and Doxil, we apply a biocomputational cancer model to study nanoparticle drug release within tumor tissue. Both tumor cells and their microenvironment are represented in this model. Based on the specific characteristics of Abraxane and Doxil, we simulate drug release and diffusion at the tumor site. With the viable tumor region modeled as approximately 100 µm in diameter from blood vessels, and using IC50 data, the paclitaxel molecules of Abraxane were found to only penetrate 73 µm deep into the tumor, while although more efficient, doxorubicin molecules of Doxil only penetrate 93 µm of the tumor viable region. Therefore, we find that the modeling predicts that in the best case scenario, the drug concentrations delivered by these nanotherapies are insufficient to kill all of the tumor cells.
Clark, Michael Christopher, "Evaluation of drug release from Abraxane and Doxil in tumor tissue." (2013). Electronic Theses and Dissertations. Paper 258.