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<https://discovery.ucl.ac.uk/id/eprint/10122302> <http://purl.org/dc/terms/title> "The exploitation of internalina fragments in drug delivery systems."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10122302> <http://purl.org/ontology/bibo/abstract> "The objective o f the work reported in this thesis was to investigate the potential of the\r\nprotein intemalin when attached to nanoparticles to secure transport across the gut wall.\r\nIntemalin, also called intemalin A or InlA, is a surface protein expressed by the\r\npathogenic bacteria Listeria monocytogenes in response to temperature and other\r\nenvironmental cues that indicate the bacterium is in a suitable host. Intemalin has been\r\nshown to interact with E-cadherin, a protein involved in structural maintenance of the\r\nepithelial cells lining the gut wall. Cadherins are found throughout the human body and\r\nthe prefix E or N etc. indicates the location where they are most commonly found, E for\r\nepithelial, N for neuronal etc. The interaction between intemalin and E-cadherin causes\r\na rearrangement of the actin cytoskeleton in the cell and this encourages the membrane\r\no f the epithelial cells to engulf the bacteria. The bacteria are then intemalised and have\r\nachieved their first step in establishing infection. Once the bacteria are inside the cell\r\nthey use a panoply of further pathogenic factors to establish and propagate the infection.\r\nIt is the specific interaction between the intemalin (or a fragment of intemalin) and the\r\nE-cadherin that this research addresses as a potential system to deliver dmgs across the\r\ngut wall as a method of targeting vectors containing the dmg.\r\nMany dmgs are still administered by injection, but non-invasive methods, including\r\noral, pulmonary, buccal, vaginal, rectal and dermal delivery, are preferred. Orally\r\nadministered dmgs are the most convenient and practical and have the highest patient\r\ncompliance. The gut wall provides a major barrier to the oral delivery of some,\r\nparticularly macromolecule pharmaceuticals. It is one o f the major physical barriers that\r\nthe immune system employs as a first line of defence against infection. There are many\r\ntools the immune system employs to protect the GI tract; the presence of normal flora to\r\ncompete for receptor sites with invaders, mucus that entraps invaders and the propulsion\r\nthat moves the mucus and thus the microorganisms and entities entrapped within it out\r\no f the body. Also the temperature, pH, digestive enzymes and patrolling immune cells\r\nhelp keep foreign entities out of the body. Pharmaceuticals that are required by the body\r\nneed to cross this barrier. Orally administered formulations achieve higher patient\r\ncompliance so this work set out to investigate a method o f employing the bacterial\r\narmament to physical carrier systems which have already been exploited experimentally\r\nin these laboratories using invasin (Hussain & Florence 1998) and tomato lectin\r\n(Hussain et al 1997).\r\n15\r\nThe effect of the intemalin protein surface adsorbed onto polystyrene nanoparticles\r\nwas investigated using the Caco-2 system. The Caco-2 cell system allows for the\r\nevaluation of drug delivery systems that will be orally administered in an isolated and\r\nrealistic, but less complex manner. This is due to their ease of cultivation and that they\r\nspontaneously differentiate into enterocyte-like cells, under normal tissue culture\r\nconditions these cell mimic the lining of the gastrointestinal tract. The study was also\r\nexpanded to include the transport and effect of incubation of different partial dendrimers\r\n(dendrons) with the Caco-2 system.\r\nThe research reported in this thesis establishes that the transport of polystyrene\r\nnanoparticles through Caco-2 cells is modified by the surface adsorption of a\r\nrecombinant version of intemalin. Further experiments indicated there was a protein\r\ninteraction between the E-cadherin and the synthesised protein."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10122302> <http://purl.org/dc/terms/date> "2005" .
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