All ETDs from UAB

Advisory Committee Chair

Derrick Dean

Advisory Committee Members

Dale Feldman

Manoj Mishra

Vinoy Thomas

Yogesh Vohra

Document Type

Dissertation

Date of Award

2014

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Enhancing therapeutic efficacy is essential for successful treatment of chemoresistant cancers such as metastatic hormone-refractory prostate cancer. Current chemotherapy regimens are plagued with issues such as toxicity, low bioavailability, and lack of specificity. To combat these issues, the feasibility of using nanodiamond particles (ND) to enhance the therapeutic efficacy of doxorubicin and resveratrol was investigated. The enhancement of chemotherapy using NDs was evaluated with three unique approaches: (1) drug mediation, (2) combination therapy, and (3) targeted drug delivery. The ND mediated doxorubicin system achieved a 50% improvement in therapeutic efficacy with over 60% cell death. The ND resveratrol combination therapy improved the efficacy of resveratrol by 40%, enhancing its typically low bioavailability. To facilitate targeting and further enhance the efficacy of doxorubicin, NDs were conjugated with the Asp-Gly-Glu-Ala (DGEA) peptide, which interacts with integrins over-expressed in metastatic prostate cancers, α2ß1. The resulting ND-DGEA doxorubicin targeted drug delivery system produced a 4 fold increase in efficacy with low drug doses. The findings from each component of the work confirmed that NDs are capable of enhancing therapeutic efficacy. The results from these studies are promising as they suggest that drug delivery with NDs provides a novel approach for decreasing toxicity and drug doses of traditional chemotherapy.

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Engineering Commons

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