A Master of Science thesis in Chemical Engineering by Saniha Aysha Ajith entitled, “A Novel Cancer Treatment Platform Utilizing Her2- Immunoliposomes And Ultrasound”, submitted in May 2020. Thesis advisor is Dr. Ghaleb Husseini. Soft copy is available (Thesis, Approval Signatures, Completion Certificate, and AUS Archives Consent Form).
Cancer is defined as the uncontrolled growth of cells in the body. It is one of the leading causes of death worldwide. One of the most common approaches to destroy cancer cells is via chemotherapy treatment, in which anti-cancer therapeutics are administered to the body. However, chemotherapy causes various adverse effects, including cardiotoxicity, nausea, anemia, and many more. To counteract these undesired effects, different smart drug delivery systems have been researched, in which nanocarriers can be used to exploit the enhanced permeability and retention (EPR) effect of cancerous tumors. Once the nanocarrier reaches the desired tumor site, external triggers can be applied to control the release of anti-neoplastic agents in that specific area. This study focuses on the use of liposomes conjugated with the monoclonal antibody, Trastuzumab, which is loaded with the chemotherapeutic drug, Doxorubicin, to target the overexpressed HER2 receptors on the surface of many breast cancer cells. Dynamic light scattering (DLS) was used to determine the liposome size, which was found to be 94.9 ± 1.29 nm for the immunoliposomes and 91.2 ± 1.47 nm for the NH2-terminated control liposomes. The concentration of lipids in the liposomes was determined using the Stewart Assay and the protein content using the BCA Assay. The external trigger used for the controlled release of the drug was low-frequency ultrasound. The release profiles of the control liposomes and immunoliposomes were studied at three different power densities, namely 7.46, 9.85, and 17.31 mW/cm2. Results showed that the immunoliposomes were slightly more sensitive to ultrasound and released a higher amount of drug in comparison to the control liposomes. Finally, drug release was modeled using nine kinetic models, namely: Zero-order, First-order, Higuchi, Hixon-Crowell, Korsmeyer-Peppas, Baker-Lonsdale, Weibull, Hopfenberg, and Gompertz. After linearizing the release data, the Baker-Lonsdale model provided the best fit. The future scope of this thesis involves using high-frequency ultrasound (HFUS) to release the drug, as well as in vitro and in vivo studies to determine the feasibility of using this drug delivery platform in hospitals and clinics around the globe.