Jani, Praful Udaykant; (1991) The uptake and translocation of nanospheres and microspheres from the rat gastrointestinal tract. Doctoral thesis (Ph.D.), University College London.

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Abstract

This thesis is concerned with the investigation of the uptake and translocation of microspheres from the rat gastrointestinal tract. The object was first to attempt to settle the controversy surrounding this topic which has arisen from the literature reports on the subject for over 30 years, as a prelude to studying the utility of microparticles as carriers for oral administration labile drug. The controversy over the possibility of the uptake of solid particles in the colloidal size range has continued for some time, some authors claiming, like Volkheimer (1965, 1978) that "persorption" occurs as a paracellular event. The present work shows that the uptake of the microspheres occurs specifically from the Gut Associated Lymphoid Tissues (GALT), namely the Peyer's Patches. Non-ionic (plain) and carboxylated (negative) fluorescent microspheres of 50nm, 100nm, 300nm, 500nm 1μm and 3μm diameters, were fed orally, by gavage (1.25mg kg-1) daily for 10 days to female Sprague Dawley rats. Peyers's patches, villi, liver, lymph nodes and spleen of animals fed the non-ionic microspheres showed unequivocal evidence of uptake and translocation of the particles, mainly restricted to the reticuloendothelial system. Heart, kidney and lungs showed no evidence of presence of microspheres. Carboxylated microspheres were taken up to a lesser degree than the non-ionised particles. Experiments with 125 I radiolabelled 100nm and 1μm particles showed a higher uptake of the smaller particles, which were concentrated in the GI tissue and liver. The microspheres were not distributed randomly in the tissues, but were concentrated at the serosal side of the Peyer's patches and could be seen traversing the mesentery lymph vessels towards the lymph nodes. The entry of the particle is gained into submucosal cells via the membraneous epithelial (M) cells which are specialized cells with a propensity to endocytosis, overlying the lymphoid follicles in the gastrointestinal and respiratory tracts. This work has shown that no 3?m microspheres were located in the major target organs eg lymph nodes, liver or spleen, after oral administration for 10 days. None was taken up by the gut or was found in the serosal layer of the Peyer's patches unlike the smaller diameter particles. Further quantitation of the presence of polystyrene in treated tissues, using Gel permeation chromatography (GPC), illustrated that the uptake and distribution of the microspheres in the systemic organs is size dependent. GPC analysis of the tissues showed the extent of uptake of 50nm particles was 34% and of the 100nm particles 26%, of which total, about 7% (50nm) and 4% (100nm), was in the liver, spleen, blood, and bone marrow. Particles larger than 100nm did not reach the bone marrow, and those larger than 300nm were absent from blood. No particles were detected in the heart or lung tissues.

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