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Characterization and Modification of Nanodiamond-Doxorubicin Complexes for Treatment of Colorectal Cancer

Abstract

Colorectal cancer is a leading cause of cancer death of the United States. Chemotherapy is a key component in the treatment of colorectal cancer. However, acquired resistance against chemotherapy and its inherent toxicity serve as major barriers to effective treatment. Nanodiamonds have been proven to overcome these barriers and can serve as a drug delivery platform for chemotherapeutics in human patients. The potential for this system needs to be explored further. In this thesis, a comprehensive study was performed on the production method of NDX (a complex of nanodiamond and doxorubicin) and its resulting physical characteristics. Ten batches of NDX were produced independently and the size and surface potential of the complexes were measured as well as their drug loading and drug release profiles. Analysis of the measurements displayed low standard deviation values across all the different parameters, illustrating a robust method for consistent production of NDX. Additionally, NDX could be further functionalized for localized treatment of colorectal cancer. Thus, NDX-loaded liposomes (NDXLPs) were synthesized. These NDXLPs were stable in conditions designed to mimic the environment in the colon and also demonstrated an ability to penetrate a protective mucus layer. Therefore, this system represents a promising method to treat colorectal cancer. Futhermore, its flexibility for customization allows it to be utilized for a broader range of applications in cancer healthcare.

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