Browsing by Author "Cramb, David Thomas"

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    Exploring the stability of polyethylene glycol functionalized nanoparticles in angiogenic blood vessels
    (2018-09-06) Sagoe, Veritas Aba Ntsifua; Cramb, David Thomas; Anikovskiy, Max; Thurbide, Kevin B.; Thangadurai, V.
    Research into the stability of liposomes as nanocarriers or nanoparticles (NPs) is well justified during an era where there is emerging research on drug delivery especially with respect to cancer. Nanoparticles face different barriers to reach their targets within a living organism which can potentially affect their stability. In this thesis, we used a systematic approach to introduce a series of liposomes (whose surfaces are partially coated with poly-ethylene glycol (PEG)) into a chicken embryo chorioallantoic membrane (CAM). The CAM was the model of choice as it is mimetic of the angiogenic vasculature present in cancerous tumors. There are fenestrations in these blood vessel walls through which NPs can pass to the tumor mass. Fluorescent liposomes were synthesized by lacing with a dye and using different proportions (2.5, 5 and 10% of the total lipid content) of PEGylated lipids (1, 2 dioleyl-sn-glcero-3phophoethanolamine-N-[Methoxy (Polyethylene glycol)-“1000, 2000 & 5000”] with molecular weights of 1000, 2000 and 5000 dalton (Da). After injection into the CAM, the time dependent behaviour is monitored using fluorescence correlation spectroscopy. The NPs were observed to agglomerate in the blood vessels. Thus, the NPs were subsequently characterized in chicken blood serum and phosphate buffered saline to ascertain the possibility of there being ionic and protein effects on the particle stability.
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    Interactions between Serum Albumin Proteins and Polystyrene Nanoparticles
    (2018-07-10) Bishop, Amanda Iris; Cramb, David Thomas; Heyne, Belinda J. M.; Ling, Chang-Chun; Harrison, Joe J.
    Nanoparticles (NPs) have become increasingly popular for several applications, especially regarding biomedical applications because of their unique properties. However, when a nanoparticle enters a biological medium, it is thought to become encapsulated in proteins and other biomolecules in a coating termed a “protein corona.” This coating is significant as it can change the identity and surface properties of the nanoparticle, thus affecting its fate within the biological medium. Studies on the formation of NP-protein complexes have been ongoing for years although the interactions are still not fully understood due to their dynamics and complexity. As a result, this hinders the use of NPs to their full potential in biomedical applications. The studies performed in this thesis analyze the interactions of fluorescent polystyrene nanoparticles (FS) of two different sizes with bovine serum albumin proteins (BSA) by the technique of Two-Photon Excitation Cross-correlation Spectroscopy (TPE-FCCS). These interactions were explored both thermodynamically and kinetically to gain insight into the formation of the early hard corona and the kinetics of the formation of the BSA-FS complexes. The results suggested very low binding ratios and a mechanism of protein association dependent on the size of the sphere present in solution. The results also suggested an irreversible formation of BSA-FS complexes, in which the BSA appears to stack at the surface of the FS. These findings are significant as they challenge the current beliefs on the formation of a protein corona and perceived monolayer formation, and furthermore, provides a deeper understanding of NP-protein interactions.