|Ph.D Thesis||Department of Mechanical Engineering|
|Prof. Haber Shimon|
|Prof. Zussman Eyal|
|Full Thesis text - in Hebrew|
A number of drug delivery platform technologies currently exist. One way of altering a drug interaction with the host is by confining the drug molecules to small vesicle packages such as liposomes. Liposomes are closed structures with sizes ranging from about 10nm to about 100?m and they are based on (phospho)lipid bilayers. They can protect a drug against degradation or protect the patient against the side effects of the encapsulated drug.
Some drugs have an optimum concentration range within which the maximum benefit is derived, while concentrations above or below this range can be toxic or produce no therapeutic benefit at all. The goal is to make a liposome to release the drug slowly while it is targeted to a certain site of interest within the body. This can be achieved through the deformation of the liposome conjugated with a specific antibody. The objective of this research is to describe the liposome deformation during its motion within different flows and to connect the deformation to the overall volume change of this liposome.
We consider an inertialess, initially spherical liposome with a thin, permeable membrane that is immersed in a viscous Newtonian creeping flow. The characteristic length of the liposome, its diameter, is large enough to neglect the Brownian motion. The viscosity ratio between inside and outside fluids is taken equal to unity.
We develop an equation which describes the coupling between the deformation and the motion of the liposome and allows one to estimate the flow rate of liquid through its membrane. The effect of elastic membrane deformation on its permeability is studied analytically in the limit of small deviations from the initial spherical liposome form. The deformed liposome shape is determined from the creeping-flow governing equations using the asymptotic method of domain perturbations. The influence of a constant electric field is also considered. The equation is solved along streamlines for several typical flows that are characterized by their elongation and shear rate-of-strain tensor components.
The results show that the volume change of liposome is determined mainly by the permeability and stiffness of its membrane and by the electrical properties of inner and outer fluids.