Karimpoor, Mahroo; (2019) Microbubble generation and application in healthcare. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The aim of this work is to investigate the application of microbubbles for targeted drug delivery and anticancer drug sensitivity investigations. Microbubbles were prepared using a microfluidic device to act as a carrier for drug delivery or building scaffolds for three-dimensional (3D) cell culture. The lifetime and bursting process of alginate microbubbles and the role of microbubbles for delivering drugs through oral administration were investigated. It was shown that the collection of microbubbles in calcium chloride solution or glycerol, along with the incorporation of gold nanoparticles into the shell of the microbubbles increased the lifetime of the microbubbles. To mimic the physiological condition, the stability of the generated microbubbles was examined under acidic pH and body temperature. Simulation of the oesophageal condition using porcine tissue showed the enhanced absorption of the drug using alginate microbubbles. This result supports the application of microbubbles for oral drug delivery to oesophageal mucosa. The other application of microbubbles in regard to anticancer drugs in this work was to measure the sensitivity of myeloid leukaemia cells to various types of antileukaemia agents in a 3D culture. A porous calcium alginate foam-based scaffold was developed using microfluidic technology. The foam-based 3D culture supported the growth and proliferation of both normal haematopoietic and leukaemia cells. The myeloid differentiation in both leukaemia and normal haematopoietic cells was enhanced in the foam-based 3D culture, compared to the 2D culture. The sensitivity of the leukaemia cell line models; K562 and HL60 and primary acute myeloid leukaemia (AML) cells to antileukemia agents; Imatinib and doxorubicin were reduced in the 3D compared to the 2D culture, which is similar to as was reported in vitro investigations. The result of this study proposes the application of calcium alginate foams as scaffold in 3D culture for antileukaemia sensitivity screens in drug discovery investigations.The other application of microbubbles in regard to anticancer drugs in this work was to measure the sensitivity of myeloid leukaemia cells to various types of antileukaemia agents in a 3D culture. A porous calcium alginate foam-based scaffold was developed using microfluidic technology. The foam-based 3D culture supported the growth and proliferation of both normal haematopoietic and leukaemia cells. The myeloid differentiation in both leukaemia and normal haematopoietic cells was enhanced in the foam-based 3D culture, compared to the 2D culture. The sensitivity of the leukaemia cell line models; K562 and HL60 and primary acute myeloid leukaemia (AML) cells to antileukemia agents; Imatinib and doxorubicin were reduced in the 3D compared to the 2D culture, which is similar to as was reported in vitro investigations. The result of this study proposes the application of calcium alginate foams as scaffold in 3D culture for antileukaemia sensitivity screens in drug discovery investigations.

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