A Master of Science thesis in Biomedical Engineering by Rand Hasan Abusamra entitled, “Using Lactose and Ultrasound to deliver chemotherapeutics”, submitted in May 2019. Thesis advisor is Dr. Ghaleb Husseini. Soft and hard copy available.
As the number of cancer patients increase, so does the number of patients that undergo chemotherapy, as well as the suffering, caused by its side effects. To solve this adversity, an innovative form of delivering chemotherapeutics and reducing their adverse effects is envisioned through the use of nanocarriers and ultrasound. Nanocarriers; dendrimers, solid lipid nanoparticles, micelles, and liposomes can be used to exploit passive targeting and the enhanced permeability and retention (EPR) effect found in cancerous tumors. For maximum accumulation at the tumor site, active targeting, and receptor-mediated endocytosis, via the conjugation of specific ligands, including carbohydrates, small molecules, proteins, and antibodies, are utilized. The controlled release of chemotherapeutics at the tumor site is then achieved by an external or internal trigger. Hepatocellular carcinoma has been found to overexpress the Asiaglycoprotein Receptor (ASGPR). Therefore, liposomes are synthesized through the lipid film hydration method and conjugated with Lactobionic acid (LA) as a targeting moiety. Infrared spectroscopy and phenol-sulfuric acid assay confirmed the attachment and molecular structure. Dynamic Light Scattering (DLS) determined the size and dispersity of the lactosylated liposome and NH2 liposomes encapsulating calcein to be 85.7±1.2 nm and 89.2±2.7 nm, respectively. Controlled release of calcein (a model drug), is achieved through low-frequency Ultrasound (US) as an external trigger at 3 power intensities of 7.46, 9.85 and 17.31 mW/cm2. The release mechanism was studied using nine different mathematical kinetic models: zero-order, first-order, Higuchi, Hixon-Crowell, Korsmeyer-Peppas, Baker-Lonsdale, Weibull, Hopfenberg and Gompertz. The release data were found to follow the Weibull model, having the highest coefficient of determination (R2). Control liposomes followed first-order release Fickian diffusion and LA liposomes had a combined release of Fickian and case II diffusion with a b-value of 1.0 and 0.91, respectively. The results of this thesis show the utility of using targeted liposomes and ultrasound in cancer treatment.