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Studies on microspheres designed for oral uptake: biocompatibility, binding and uptake mechanisms

Carreño-Gómez, Begoña; (1999) Studies on microspheres designed for oral uptake: biocompatibility, binding and uptake mechanisms. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

This thesis deals with the investigation of two types of polymer microspheres designed for oral uptake in the gastrointestinal tract. The first two results chapters (Chapters 2 and 3) are concerned with the preparation and characterisation of chitosan microspheres loaded with three model proteins, horseradish peroxidase, β-amylase and invertase with the objective of targeting lymphoid tissue. The initial aim was to study the interaction of hydrophilic and biodegradable polymer microspheres, with and without encapsulated antigens, with M-cells present in the Peyer's patches. Biocompatibility studies were performed on this delivery system (Chapter 3), and they caused 100% loss of cell viability at all concentrations used (0.1 to 3 mg/ml). Further studies with these particles were thus abandoned. The in vitro biocompatibility of seven soluble chitosan polymers was then systematically studied by evaluating cytotoxicity towards B16F10 cells and the ability to lyse rat erythrocytes. Cytotoxicity towards B16F10 was concentration dependent and varied according to the salt used and polymer molecular weight. The ranking of cytotoxicity was: chitosan hydrochloride>chitosan hydroglutamate>glycol chitosan> chitosan hydrolactate. In the lysis assay, release of haemoglobin occurred on exposure to all soluble chitosans in a time dependant manner. Subsequently microspheres made of a non-biodegradable polymer such as polystyrene were used in order to be able to trace their uptake through the gut wall, with the aim of elucidating the biology behind particle translocation. Chapter 4 details how microspheres conjugated to two different ligands. Tomato lectin (TL) and Bovine serum albumin (BSA) were prepared (both proteins having similar molecular weight) and characterised. The uptake of conjugated microspheres was determined in vitro using a rat everted intestinal technique (Chapter 5). Uptake was shown to be linear with time and concentrations used. TL conjugates tissue accumulation was three times that of BSA conjugates, whereas transfer to the serosal side was two times higher. TL conjugates were absorbed by receptor mediated endocytosis; transfer to the serosa being 95% reduced by a TL inhibitor. Finally, preliminary studies using the Caco-2 (human adenocarcinoma) cell line, corroborated the specificity of TL conjugated microspheres binding to the intestinal epithelium.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Studies on microspheres designed for oral uptake: biocompatibility, binding and uptake mechanisms
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10110840
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