An Investigation of The Use of Dendrimer-Based Carrier to Cross Cellular BarrierReport as inadecuate






Author: Hueyminn (Stephanie) Teow

Source: https://core.ac.uk/

Dendrimers are a novel class of highly branched polymers with a high degree of uniformity and monodispersity. As a result of the unique properties and characteristics of dendrimers, they have found a wide range of pharmaceutical applications. This study investigated the ability of polyamidoamine (PAMAM) dendrimer-based drug delivery systems to enhance the permeability of a drug that is a substrate of P-glycoprotein (P-gp) efflux transporter with low water solubility. This thesis described the syntheses, characterisations and biological evaluations of the dendrimer-based drug delivery system to overcome the cellular barriers.ud ud G3 PAMAM dendrimers were conjugated with lauryl chains via a carbamate bond. Paclitaxel, a low water solubility P-gp substrate and anti-tumour drug, was conjugated to G3 and/or lauryl-G3 PAMAM dendrimer conjugates via a glutaric anhydride linker. Unmodified G3 PAMAM dendrimer and all the dendrimer co...


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AN INVESTIGATION OF THE USE OF DENDRIMER-BASED CARRIER TO CROSS CELLULAR BARRIERS By HUEY MINN TEOW A thesis submitted to the University of Central Lancashire in partial fulfilment of the requirements for the degree of Doctor of Philosophy October 2010 TABLE OF CONTENTS TABLE OF CONTENTS.
2 LIST OF FIGURES .
8 LIST OF TABLES .
12 ABSTRACT .
13 DECLARATION.
16 COPYRIGHT STATEMENT.
17 ACKNOWLEDGEMENTS.
18 ABBREVIATIONS .
19 CHAPTER 1: INTRODUCTION .
21 1.1 DRUG DELIVERY ACROSS CELLULAR BARRIERS .22 1.2 MECHANISM OF INTESTINAL BARRIER ABSORPTION .23 1.2.1 1.2.1.1 Passive transcellular diffusion.25 1.2.1.2 Carrier-mediated transport .26 1.2.1.3 Endocytosis- Vesicular transport.27 1.2.2 1.3 Transcellular pathway .25 Paracellular pathway .27 TRANSPORT ACROSS THE BLOOD-BRAIN BARRIER .28 1.3.1 1.3.1.1 1.3.2 The blood-brain barrier .29 Tight junctions .32 Therapeutic pathways across the blood-brain barrier .34 1.3.2.1 Transcellular lipophilic pathway.35 1.3.2.2 Carrier-mediated transport .36 1.3.2.2.1 P-glycoprotei....





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