Liposomes have the ability to carry and deliver both hydrophilic and hydrophobic drugs and to protect them when injected into the circulatory system. They thus provide an attractive vehicle for drug delivery. However, problems of rapid clearance and inability to target liposomes to specific cells and tissues remain unresolved. Rapid clearance has been attributed to adsorption of opsonins, and one approach to reduce such adsorption is to create sterically stabilized liposomes by modifying the surface with polyethylene glycol (PEG) or dextran. To deliver their drug "payload" liposomes must interact with the membranes of target cells. Interactions with cellular components of the vascular walls have been observed for various sulfated polysaccharides such as heparin and functionalised dextrans. Based on the above considerations, the purpose of this work was to investigate the ability of various polymeric modifiers on liposomes to reduce protein adsorption and promote incorporation into target cells. Liposomes of composition PC/PEI cholesterol (70/10/20 mol %) were surface modified with PEG, dextran, heparin, and functionalised dextran. Protein adsorption was studied from solutions of IgG in buffer and from plasma. Adsorption from buffer was measured by radio labelling methods. For the plasma work, a total protein assay was used to determine the amount of protein adsorbed to the liposome surface, while gel electrophoresis and immunoblotting methods were used to examine the profiles of protein binding. Liposome incorporation into vascular smooth muscle and endothelial cells was evaluated using fluorescent labelling and radio labelling techniques. The IgG adsorption studies showed reduced adsorption on all polymer-modified liposomes. Plasma adsorption data showed that adsorbed protein layer compositions on the different liposome types were similar, but different from that of the plasma itself, showing that the plasma was fractionated on the liposome surfaces. Cell interaction studies showed that liposomes modified with dextran and sulfated dextran were incorporated into both cell types. The unmodified, PEG-and heparin-modified liposomes were not incorporated to any significant extent. / Thesis / Master of Engineering (ME)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/24558 |
| Date | 12 1900 |
| Creators | Savoie, Anne-Marie |
| Contributors | Brash, J. L., Chemical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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