Model membranes for drug-membrane interaction studies

Author: Daniel K. Suhendro

Suhendro, Daniel K., 2018 Model membranes for drug-membrane interaction studies, Flinders University, School of Chemical and Physical Sciences

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Abstract

Many model membranes have been developed and used to simplify the study of the processes that happen on the cell membrane. One of the processes is drug-membrane interaction. Studying drug-membrane interaction is important because many drugs have been designed to either interact with a cell membrane component or to pass through the membrane into the cell.

In the first part of this work drug-membrane interaction was studied using tethered bilayer lipid membrane (tBLM) as the model membrane and CPZ (Chloropromazine) as the model drug. The aim of the study was to determine the mechanism of drug binding and accumulation on the membrane. The result of the interaction study showed that accumulation of drugs on the membrane did not depend on the free binding sites on the membrane but rather on the concentration of the free drug. This trend did not continue forever but there was a limit in which no more drugs could bind to the membrane. The limit was indicated by overshoots where at first the amount of drug binding to the membrane increase quickly but then decreased more slowly.

In the second part of this work, a three dimensional model membrane was developed. This three dimensional model was a spherical tBLM with gold nanoparticle core to anchor the tethered lipids. This model membrane, a tethered liposome coated gold nanoparticles should be more stable than liposomes. This is the aim of the second part in this work, to synthesise a novel model membrane consisted of gold nanoparticle core coated with liposomes in which the inner layer of lipids are tethered to the core by tethered lipid molecules.

The constructs were to be made in three stages: first is the synthesis of gold nanoparticle, second is the functionalisation of the nanoparticle with thiolipids and third coating the thiolipids with lipid. Although the aim was to make tethered lipid bilayer to the gold nanoparticle core, this cannot be fully realised. What was finally achieved was the assembly of gold nanoparticle functionalised with thiol molecules and coated with lipids. This work is still in the proof of concept stage and further work need to be done to synthesise the tethered liposome model membrane.

Overall, this thesis contributes to the research of drug-membrane interaction, particularly on the binding and accumulation of drugs to the membrane. It also contributes to the attempt to synthesise a novel model membrane that can further advance the research in drug-membrane interaction as well as drug carriers.

Keywords: drug-membrane interaction, tBLM, tethered lipid bilayer membrane, chlorpromazine, CPZ, drug binding, liposome, gold nanoparticle, AuNP, tethered liposome

Subject: Chemistry thesis

Thesis type: Doctor of Philosophy
Completed: 2018
School: School of Chemical and Physical Sciences
Supervisor: Assoc. Prof Ingo Koeper