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Doxorubicin-encapsulated Albumin liposomes with acoustic triggering for cancer treatment

Farooq, Afifa
A Master of Science thesis in Biomedical Engineering by Afifa Farooq entitled, “Doxorubicin-encapsulated Albumin liposomes with acoustic triggering for cancer treatment”, submitted in May 2019. Thesis advisor is Dr. Ghaleb Husseini. Soft and hard copy available.
With cancer being the leading cause of death worldwide, increasing economic and social resources are being directed by researchers and healthcare professionals to treat the disease, or at least provide palliative care to patients that cannot be treated due to advanced cancerous growth. While the end goal of all the cancer-related research is its cure, current technology is focused on the creation of smart drug delivery systems (DDS) that aims to diagnose and treat cancer. For effective design of these systems, chemotherapeutic agents are combined with carriers, which evade the immune response, to achieve desired drug release amounts and rates through ligand-targeting and external release stimuli. This work provides a literature review that aims to lay the groundwork for development of the following DDS: Albumin-bound stealth liposomes encapsulated in the chemotherapeutic drug, doxorubicin, with ultrasound-triggered drug release for the treatment of breast and pancreatic cancer. Experimental work was carried out involving the synthesis and characterization of the liposomes, along with nine model fitting exercises to determine the best fits for experimental data. Large unilamellar vesicles for control and albumin-bound liposomes, with sizes of 86.01 ± 2.97 nm and 86.17 ± 2.956 nm, respectively, were synthesized. Drug release by 20 kHz pulsed ultrasound release was carried out at low intensities with maximum releases of 90.25% at 20% intensity, 95% at 25% intensity, and 99.7% at 30% intensity for control liposomes, followed by 78.53%, 88.41%, 96.27% at the respective intensities for albumin-liposomes obtained over a period of 3 minutes. Albumin-liposomes were found to be more stable with doxorubicin encapsulation as opposed to calcein encapsulation. In addition, model fitting revealed the Korsmeyer-Peppas and Higuchi models as the best fits for doxorubicin-liposomes; while the Korsmeyer-Peppas and Weibull models were found to better predict calcein-liposome drug release behavior. Analysis of the release exponents, from Korsmeyer-Peppas linear regression, showed that both doxorubicin and calcein liposomes exhibited anomalous drug release kinetics.
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