Title page for ETD etd-06152011-092059


Document Type Doctoral Thesis
Author Lemmer, Yolandy
Email ylemmer@csir.co.za
URN etd-06152011-092059
Document Title Assessment of mycolic acids as ligand for nanoencapsulated anti-tuberculosis drug targeting
Degree PhD
Department Biochemistry
Supervisor
Advisor Name Title
Dr H Swai Co-Supervisor
Prof J A Verschoor Supervisor
Keywords
  • nano-encapsulated anti-tuberculosis drug
  • M. tuberculosis
Date 2011-04-07
Availability unrestricted
Abstract
South Africa currently has the highest incidence of TB per 100 000 people in the world. In 2007 alone 112 000 people died of TB in South Africa, of which 94 000 were co-infected with HIV. Although TB treatments exist, poor patient compliance and drug resistance are challenges to TB management programs worldwide. Here, this challenge was addressed by the development of a polymeric anti-TB nanodrug delivery system for anti-TB drugs that could enable entry, targeting and sustained release for longer periods, hence reducing the dose frequency and simultaneously improve patient compliance. The aim was to prepare functionalised polymeric nano drug delivery vehicles to target TB infected macrophage cells. Successful nano encapsulation of anti-TB drugs was achieved and uptake of the antibiotics in the cells, demonstrated. A possible targeting agent, mycolic acids (MA) from M. tuberculosis was explored. The MA incorporated into nanoparticles could possibly serve as a ligand for cholesterol-rich areas, due to the cholesteroid nature of MA and the fact that MA is attracted to cholesterol. In another targeting scenario, MA incorporated into nanoparticles may interact with the anti-mycolic acid antibodies that are anticipated to be present in higher concentrations at the infected areas. The cholesteroid nature of MA was confirmed and how it related to the fine structure of the MA. The prepared MA containing nanoparticles were shown in vitro to be taken up in macrophage cell lines, without the MA hindering the uptake of the particles. In terms of toxicity, nanoparticles with or without MA were found to be acceptable for use, although MA did affect the viability of the cells more than poly, DL, lactic-coglycolic acid particles alone in in vitro studies. This paves the way for testing MA as a ligand to target anti-TB drugs to the sites of infection in human TB patients.

2010 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.

Please cite as follows:

Lemmer, Y 2010, Assessment of mycolic acids as ligand for nanoencapsulated anti-tuberculosis drug targeting, PhD thesis, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-06152011-092059/ >

D11/441/ag

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  01chapter1.pdf 1.50 Mb 00:06:56 00:03:34 00:03:07 00:01:33 00:00:07
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  07appendix-B.pdf 2.54 Mb 00:11:46 00:06:03 00:05:17 00:02:38 00:00:13
  08appendix-C.pdf 4.74 Mb 00:21:56 00:11:16 00:09:52 00:04:56 00:00:25

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