Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.482091
Title: Lectins in drug delivery to the oral cavity.
Author: Nantwi, Paul Kwasi Kankam.
ISNI:       0000 0001 3439 4624
Awarding Body: University of Portsmouth
Current Institution: University of Portsmouth
Date of Award: 1997
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Abstract:
Lectins are proteins or glycoproteins of non-immune origin, capable of specific interaction with, and reversible binding to carbohydrate moieties of complex glycoconjugates. Lectins are ubiquitous in nature and are present in all living organisms. In nature lectins are implicated in cell recognition and adhesion processes, and have been described as "second generation" mucoadhesives. The aim of this project was to identify lectins that could be incorporated into dosage forms to allow their retention within the oral cavity. This would allow prolonged localised drug delivery. Initial screening studies on human buccal cells, usmg the avidin-biotincomplex/ diaminobenzidine method suggested that all the lectins tested appeared to bind to varying degrees, as visualised by a diaminobenzidine (DAB) precipitate to the oral epithelial surface. The stain intensities were analysed semi-qualitatively with E micro densitometer GN5 (Barr and Stroud). A substantial reduction in lectin binding was observed after exposing buccal cells to a series of lectin solutions pre-treated with secretor and non-secretor saliva. However when bound to the buccal cells, there was little displacement of lectins on exposure to either saliva types. Kinetic binding studies revealed the presence of the lectins from Pisum sativum and Arachis hypogaea, after only 20 s contact. There were some differences in lectin binding evident between rat oral tissue and human buccal cells, but those that bound avidly to both were selected for furthe studies. In order to allow a quantitative assessment of binding, the lectins from Canavali ensiformis, Arachis hypogaea and Triticum vulgaris were labelled with Technetium-99n (Tc-99m) using a cyclic diethylenetriamine pentaacetic acid conjugation technique. In this preliminary study it was found that 1.18 fmoles of the Canavalia ensiformis lectir 3.27 fmoles of the Arachis hypogaea lectin and 11.11 fmoles of the Triticum vulgari lectin bound per buccal cell. This was reduced when Tc-99m-labelled Canavali ensiformis lectin was inhibited by the presence of 40% w/v glucose solution. It was estimated that a therapeutic dose of a potential dosage form could be conjugated to the Triticum vulgaris lectin within the oral cavity, thus demonstrating the feasibility of using this, and possibly other lectins in a drug delivery strategy. Preliminary in vivo studies in the conscious rat model suggested that the Tc-99m-labelled Canavalia ensiformis an Triticum vulgaris lectins were present within the oral cavity, 1 hand 2 h respectively after application, with about 25% of the Canavalia ensiformis lectin being lost into the stomach through swallowing. Transmission electron microscopy studies were initiated to determine the exact sites of lectins binding to the human buccal cell. Fresh, unfixed human buccal cells were incubated in a solution containing 20 nm gold-labelled Canavalia ensiformis lectin. was found that after processing, the lectin bound to the external surface of the buccal cells, or to external mucin. No binding was observed when pre-fixed human buccal cells were used, indicating that fixation affects the glucose/ mannose-containing binding site Canavalia ensiformis lectin binding to the buccal cells was partially inhibited by the presence of glucose, the hapten sugar. It was concluded that lectins will bind to the rat oral epithelial and human buccal cell surfaces to varying degrees, and will persist, even in the presence of saliva. In particular the lectin from Triticum vulgaris was shown to have good stability in the conscious rat model for up to 2 h, and shows great promise for use in a potential lectin-containing drug delivery system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.482091  DOI: Not available
Keywords: Buccal; Biotin; Saliva
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