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Synthesis of Estrone Liposomes Using Microfluidics
Agam, Mohamed Abdalla
Agam, Mohamed Abdalla
Date
2022-05
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Thesis
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Description
A Master of Science thesis in Biomedical Engineering by Mohamed Abdalla Agam entitled, “Synthesis of Estrone Liposomes Using Microfluidics”, submitted in May 2022. Thesis advisor is Dr. Mohamed Abdelgawad and thesis co-advisor is Dr. Ghaleb Husseini. Soft copy is available (Thesis, Completion Certificate, Approval Signatures, and AUS Archives Consent Form).
Abstract
Liposomes consist of bilayer lipid membranes that can encapsulate drugs in the internal hydrophobic part of the hydrophilic bilayer. In targeted drug delivery, liposomes are used as nanocarriers to deliver and target certain diseases to avoid side effects. Instead of using chemotherapy, treating breast cancer can be done using targeted drug delivery by using Estrone conjugated liposomes that will reach the tumor site due to the receptors found on the membrane and nucleus of the cancer cells. Estrone liposomes can be synthesized using conventional techniques such as the thin-film hydration method. Conventional techniques have limitations in controlling the liposomes size and size distribution. Microfluidics, which is a novel technology enabling liquid manipulation on the microscale, was recently used in the synthesis of liposomes. It offers many advantages over conventional techniques, such as smaller liposome size, better uniformity, and reproducibility. In this thesis a herringbone micromixer microfluidic chip was used for the synthesis of estrone liposomes. Using this chip, a solvent stream containing the lipids was mixed with another stream of Phosphate buffer saline (PBS) inside a microchannel integrated with herringbone-shaped ridges that enhances mixing of the two streams. The small size scale involved enabled rapid solvent exchange and initiated the self-assembly of the lipids to form the required liposomes. The effect of different parameters affecting liposome size, such as ratio between the flow rate of the solvent and the buffer solutions (FRR), total flow rate, lipid concentrations and solvent type were investigated. Using this technique, liposomes as small as 132 nm in diameter were prepared on device without the need for any further processing. Calcein was encapsulated inside the prepared liposomes as a model drug and was released under the effect of applying ultrasound waves at different powers as exhibited in conventionally prepared liposomes. Size stability of the prepared liposomes was tested over a period of one month without a considerable change in liposomes size. The novalety of this work is the synthesis of Estrone-liposomes using a microfluidics device, which is the first thesis to use a microfluidics technique to synthesize targeted liposomes conjugated with estrone. Overall, using microfluidics for synthesis of Estrone-liposomes offered unique advantages over traditional techniques for targeted liposomes synthesis including a simpler setup and full ability to reproducibly control size of the produced liposomes.