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Synthesis of PAMAM dendrimers and investigations of their interaction with POPC/POPG lipids

Synthesis of PAMAM dendrimers and investigations of their interaction with POPC/POPG lipids
Synthesis of PAMAM dendrimers and investigations of their interaction with POPC/POPG lipids
PAMAM dendrimers are three dimensional organic polymers synthesised by repetitive steps to achieve a controlled size and shape with a choice of surface functional groups. One of the potential applications of dendrimers is for drug/gene delivery which requires the dendrimer to interact with the cellular membranes. This study is designed to probe the interactions between PAMAM dendrimers and lipid bilayers. To investigate these interactions PAMAM dendrimers up to the third generation were synthesised. 31P and 1H-1H NOESY NMR studies between these dendrimer and POPC/POPG-derived lipids were then carried out. The results obtained from the NMR experiments were then compared with those from fluorescence studies using a surface labelled PAMAM dendrimer and the nature of the dendrimer-lipid bilayer interactions was also explored using molecular dynamics modelling. The solid-state NMR study in a controlled buffer at pH 7.2 revealed that the larger dendrimer (third generation) interacts strongly with a bilayer containing POPG, but not with a bilayer containing only POPC, and no interaction between the smaller dendrimer (zero generation) was observed with either POPC or POPG. This was confirmed with the fluorescence experiments, as changes in the emission intensity of a labelled dendrimer were mainly detected for negatively charged species (SDS and POPG) and rather less for zwitterionic, neutral or cationic species (1,2-dodecyldiol, CTAB and POPC). The coarsegrained molecular dynamic simulations showed that the 3rd generation PAMAM dendrimer can interact with the surface of the membrane when dendrimer is positively charged, but not when the dendrimer is uncharged. These studies demonstrate how the positive charges and size of the dendrimer influence the interaction with negatively charged lipid, which can have an impact on both the dendrimer’s cellular uptake and potential toxicity..
Gneid, Hassan
1f4ee688-0336-495e-b112-3309387d8076
Gneid, Hassan
1f4ee688-0336-495e-b112-3309387d8076
Grossel, Martin
403bf3ff-6364-44e9-ab46-52d84c6f0d56

Gneid, Hassan (2014) Synthesis of PAMAM dendrimers and investigations of their interaction with POPC/POPG lipids. University of Southampton, Chemistry, Masters Thesis, 132pp.

Record type: Thesis (Masters)

Abstract

PAMAM dendrimers are three dimensional organic polymers synthesised by repetitive steps to achieve a controlled size and shape with a choice of surface functional groups. One of the potential applications of dendrimers is for drug/gene delivery which requires the dendrimer to interact with the cellular membranes. This study is designed to probe the interactions between PAMAM dendrimers and lipid bilayers. To investigate these interactions PAMAM dendrimers up to the third generation were synthesised. 31P and 1H-1H NOESY NMR studies between these dendrimer and POPC/POPG-derived lipids were then carried out. The results obtained from the NMR experiments were then compared with those from fluorescence studies using a surface labelled PAMAM dendrimer and the nature of the dendrimer-lipid bilayer interactions was also explored using molecular dynamics modelling. The solid-state NMR study in a controlled buffer at pH 7.2 revealed that the larger dendrimer (third generation) interacts strongly with a bilayer containing POPG, but not with a bilayer containing only POPC, and no interaction between the smaller dendrimer (zero generation) was observed with either POPC or POPG. This was confirmed with the fluorescence experiments, as changes in the emission intensity of a labelled dendrimer were mainly detected for negatively charged species (SDS and POPG) and rather less for zwitterionic, neutral or cationic species (1,2-dodecyldiol, CTAB and POPC). The coarsegrained molecular dynamic simulations showed that the 3rd generation PAMAM dendrimer can interact with the surface of the membrane when dendrimer is positively charged, but not when the dendrimer is uncharged. These studies demonstrate how the positive charges and size of the dendrimer influence the interaction with negatively charged lipid, which can have an impact on both the dendrimer’s cellular uptake and potential toxicity..

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Published date: 20 October 2014
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 375124
URI: http://eprints.soton.ac.uk/id/eprint/375124
PURE UUID: ee8e3568-60e4-401b-af2e-80951be6540c
ORCID for Martin Grossel: ORCID iD orcid.org/0000-0001-7469-6854

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Date deposited: 22 Jun 2015 09:39
Last modified: 06 Jun 2018 13:09

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Contributors

Author: Hassan Gneid
Thesis advisor: Martin Grossel ORCID iD

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