A Master of Science thesis in Chemical Engineering by Amal Elsadig Elamir Ahmed entitled, “Ultrasound triggered release of Trastuzumab-conjugated immunoliposomes targeting breast cancer”, submitted in December 2018. Thesis advisor is Dr. Ghaleb Husseini and thesis co-advisor is Dr. Rana Sabouni. Soft and hard copy available.
Cancer is one of the deadliest diseases in this era. Since conventional treatment has many side effects, its use is limited, which augments the need for new smart drug delivery systems, such as nanocarriers, capable of shielding the healthy cells from the adverse side effects of chemotherapy. To this endeavor, liposomes are the most widely used and researched nanovehicles in the fight against cancer. They can be engineered to specifically target cancer cells by modifying their surface with targeting moieties. In this thesis, Trastuzumab was used as the targeting moiety for HER2-positive breast cancer. Once these drug-loaded liposomes reach the tumor, their release can be triggered using ultrasound, an external modality capable of accelerating the cytotoxic effects of the drug. The purpose of this study is to test the ultrasound-triggered release of calcein (a model drug) from immunoliposomes and compare it with the control (non-targeted) liposomes, under the utility of low-frequency ultrasound. The overall goal is to obtain an engineered immunoliposomes that specifically targets malignant tissue using acoustic power. The liposomes were categorized to be unilamellar vesicles (ULVs) with average radii of 89 nm and 101 nm for non-targeted liposomes and immunoliposomes, respectively. Next, the attachment of Trastuzumab was confirmed resulting in 9 Trastuzumab molecules per liposome. Low-frequency ultrasound (at 20 kHz) results showed the sono-sensitivity of both carrier types, with immunoliposomes being more acoustically sensitive, releasing 92% of the model drug, compared to 86% released from NH2 liposomes. Results also showed an increase in the release rate as the power density increased from 7.46 to 17.31 (mW/cm2). Finally, both types of liposomes were tested for their release kinetics, and results showed adherence to the Korsmeyer-Peppas model with an n > 0.45 which indicates a non-Fickian diffusion of the drug through the liposomal membrane. Statistical analysis showed that the release rate constants were significantly different at different power densities. Release rates (kkp) at 7.46 (mW/cm2) for immunoliposomes and NH2 liposomes were 2.098 x 102 and 2.094 x 102, respectively. Using ultrasound and targeted liposomes, we envision a drug delivery system capable of reducing the side effects of conventional chemotherapy.