UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Synthesis and evaluation of dendrimers as potential carrier systems

Sakthivel, Thiagarajan; (1998) Synthesis and evaluation of dendrimers as potential carrier systems. Doctoral thesis (Ph.D), UCL (University College London). Green open access

[thumbnail of Synthesis_and_evaluation_of_de.pdf] Text
Synthesis_and_evaluation_of_de.pdf

Download (9MB)

Abstract

The successful delivery of bioactive molecules by the oral route represents a major challenge. One approach to enhance the oral uptake of these moieties is to exploit the phenomenon of particulate uptake across the GI tract, by means of nanoparticulate carriers. This thesis examines the development of some novel dendrimers as an approach in the search for carriers which are more extensively taken up than large polymeric structures and investigating the physical properties of some synthetic dendrimers. Their biodistribution and use as a non-viral vector for the gene delivery were also investigated. A group of dendrimers with lipidic terminals were synthesised ranging from C40 to C1404 with molecular weights from 737 (1st generation) to 25,246 (6th generation). The area per molecule of these dendrimers ranged between 0.41 nm2 and 16.1 nm2. A reasonably linear correlation between the logarithmic area/molecule in nm2 and the logarithmic molecular weight of dendrimer generations was observed. Linear correlation was also observed with the projected area of dendrimers by computer generated molecular model and area/molecule observed by surface pressure studies. One of the dendrimers synthesised was found to form the supramolecular aggregates. The biodistribution of this dendrimer have been studied after oral administration. Good uptake of dendrimer after oral administration was observed. Lymphoid uptake studies indicated the preferential uptake of this dendrimer (per gram tissue) through lymphoid small intestine than through the non-lymphoid small intestine after 3 h and 12 h. In the large intestine uptake through the non-lymphoid large intestine was always higher than through lymphoid large intestine, which may be due to the limited availability of Peyer's patches. For gene delivery, a group of dendrimers with free amino groups was synthesised. To study the effect on transfection efficiency our strategy focussed on (i) the presence and/or number of amino groups, (ii) the length of the linker chain, (iii) the attachment of a sugar unit to the dendrimer and (iv) the position of attachment of the lipid moiety. In addition, we have synthesised peptide dendrimers containing a nuclear localisation signal sequence to enhance transgene expression in vitro.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Synthesis and evaluation of dendrimers as potential carrier systems
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Drug delivery
URI: https://discovery.ucl.ac.uk/id/eprint/10105074
Downloads since deposit
65Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item