Nasseri, Behrooz; (2003) Microfabrication of vesicular systems into micro- and nano- structures. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The thesis explores the effect of manipulation of the structures of lipid and surfactant vesicles (liposomes and niosomes). After an introduction to the microfabrication of delivery systems the thesis is divided into five chapters dealing with the fabrication from polyhedral niosomes of novel microtubules, some properties of extruded non-ionic surfactant microtubules, the physico-mechanical properties of vesicular membranes, the micromanipulation of vesicular membranes and their tethers and finally some conclusion are drawn about the direction of future work. Polyhedral niosomes (5 - 20 μm in diameter) prepared from different non-ionic surfactants were extruded under controlled pressure from glass capillaries (˜ 1 μm in diameter), fusing into three distinct microtubule morphologies reflecting their plastic nature: simple microtubules, concentric ("whorl") structures and vesicles inside microtubules. The formation of these structures is investigated, with further manipulative investigation of their robustness, polymerisation of monomers in tubules and act as model systems inter alia for the transport of solid latex particles, and of vesicles in capillaries. The effect of extrusion on the loss of encapsulated carboxyfluorescein (CF) from giant polyhedral vesicles (5 - 20 μm in diameter) passing through micropipette apertures was investigated as a function of exit diameter (1-4 μm). Furthermore, the release of CF from various microtubules produced from two types of non-ionic surfactant vesicles with different diameters over a period of 5 h was studied. The effect of temperature on the release profile of the microtubules was also explored. Physicomechanical studies on spherical liposomes and niosome membranes were carried out by deformation of spherical vesicles inside narrow micropipettes under defined pressures where the shear modulus of surface elasticity of the vesicles was obtained as a function of temperature. Micromanipulation of the vesicle membrane bilayers allowed a systematic peeling of the outer bilayers of the vesicles. A more invasive micromanipulation of the vesicle bilayers allowed the separation of an entrapped vesicle from the parent vesicle yielding two separate vesicles. Furthermore, the effect of entrapped dye on the membrane viscoelasticity was also studied with liposomes containing carboxyfluorescein and Rhodamine B. The latter showed a rigidifying effect on the membrane after two weeks storage, to the extent that tether formation or systematic peeling of their membrane was no longer possible. While studying vesicle tethers, the transport of the parent vesicle inside bipolar tethers formed from outer bilayers was observed, and serendipitously a novel mechanism of vesicle movement was discovered. Movement of vesicles within tethers is determined by the differences in the surface energies created in the tether propelling the vesicle in the opposite direction to tether retraction. Finally bifurcation of tethers into complex tether networks and tether rupture as well as tether adhesion to spherical vesicles and solid latex microspheres were phenomena also investigated.

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