Ross, Callum and Allsop, David and Fullwood, Nigel (2020) The development of antibody loaded liposomes for the treatment of Alzheimer's Disease. Masters thesis, Lancaster University.
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Abstract
Purpose: To investigate the incorporation of antibodies into the hydrophilic core of liposomes. This includes studying the development of antibody incorporation techniques, the impact antibody incorporation has on the size and shape of liposomes, and the ability for antibody loaded liposomes (AB-NLs) to penetrate SH-SY5Y neuroblastoma cells, giving insight into whether these types of liposomes can be used to delivery antibodies into cells. Methods: Antibodies were incorporated in the hydrophilic core during liposome preparation. Regular liposomes were then produced using a mini extruder, and then further processed for additional modifications. Analysis of liposome size and polydispersity index (PDI) was obtained by Dynamic Light Scattering (DLS), and then Transmission Electron Microscopy (TEM) was used to analyse the ultrastructure, size and lamellarity of formed vesicles. The Wako Assay measured the quantification of sphingomyelin in liposomes, which could then be used to produce liposomes with known lipid content. The ability for AB-NLs to penetrate SH-SY5Y cells was observed by a cell penetration assay. Results: AB-NLs had a tendency to clump, but were otherwise stable. Antibody incorporation was successful, yet efficiency was poor. AB-NLs were delivered into SH-SY5Y cells, enhanced by TAT attachment and Antibody fluorescence was observed. Conclusion: Development of current antibody incorporation techniques is essential for improved uptake. There is potential for AB-NLs as a therapeutic treatment with additional research.