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Nanostructured surfaces created by the interactions of dendrimers and oppositely charged amphiphiles

Yanez, Marianna LU (2014)
Abstract (Swedish)
Popular Abstract in English

Popular Science Abstract

In our daily routines, we use products and come across applications that involve mixtures of polymers and small amphiphilic molecules in water, for example detergents, pharmaceutics, foodstuffs, shampoos and paints. Polymers are very large molecules formed by smaller units that are repeated and connected. Amphiphilic molecules contain both one part which is ‘water loving’ (hydrophilic) and one part that is ‘water hating’ (hydrophobic). The polymer/amphiphile combination is used to control the stability and efficacy of the products mentioned above.

One type of polymer that has drawn a lot of attention is dendrimers. They have a very interesting shape... (More)
Popular Abstract in English

Popular Science Abstract

In our daily routines, we use products and come across applications that involve mixtures of polymers and small amphiphilic molecules in water, for example detergents, pharmaceutics, foodstuffs, shampoos and paints. Polymers are very large molecules formed by smaller units that are repeated and connected. Amphiphilic molecules contain both one part which is ‘water loving’ (hydrophilic) and one part that is ‘water hating’ (hydrophobic). The polymer/amphiphile combination is used to control the stability and efficacy of the products mentioned above.

One type of polymer that has drawn a lot of attention is dendrimers. They have a very interesting shape constituted by a core with a well-defined number of branches distributed symmetrically in a structure that resembles a tree. Their synthesis is performed by a series of steps and with each step a new generation is formed which means that a certain number of new branches is added and the size of the dendrimer increases. The ends of the branches can be varied to give these molecules different functions, for example they can carry electrical charges to be attracted to molecules and surfaces of opposite charge.

The ramifications of the structure of dendrimers are important because the density of the branches is larger at the surface of the molecule than in the core, and this feature can be exploited to encapsulate smaller molecules, for example medicines, within its interior to deliver them to a specific place in the body. Another important medical application of dendrimers is the condensation and delivery of DNA in the body, which is exploited in therapeutic treatments and it is known as gene therapy.

The aim of this thesis was to reveal the interactions between dendrimers that have positive charges on their surface and small amphiphilic molecules that have a negative charge. The behavior of the mixtures was examined at the solid-liquid and air-liquid interfaces, and this work was motivated by two main points: (i) their function in the applications mentioned previously relies on the properties of these mixtures at interfaces and (ii) the techniques employed to probe surfaces are very sensitive and yield precise information about the structure and composition. The dendrimers chosen in this thesis are called poly(amidoamine) (PAMAM) and they are considered one of the most functional type of dendrimers synthesized so far. Three different sizes were studied, which from small to large were generations 2, 4 and 8.

The first part of the research concerns the interactions of PAMAM dendrimers with the negatively charged surfactant sodium dodecyl sulfate (SDS). A surfactant is a type of amphiphilic molecule and its name reflects its ability to adsorb readily at surfaces (surfactant = surface active agent). SDS is one of the most employed surfactants in commercial products such as detergents and shampoos. The mixtures were investigated at the silica-water and at the air-water interfaces in relation to the bulk solution behavior. Silica (silicon dioxide) has a negative charge under the conditions employed in our experiments and therefore the dendrimer adsorbs to the surface but the surfactant is repelled. It was found that the dendrimer generation, the bulk composition (or dendrimer/surfactant ratio) and the method of adsorption can be varied to control the structure and composition of the layers formed on the solid surface. This could be useful for the development of applications such as molecular sensors or the encapsulation of small molecules like dyes at surfaces.

At the air-water interface, the dendrimer alone does not adsorb but the surfactant does. In this case, the adsorption from the mixtures was largest for the smallest dendrimer (generation 2). The bulk composition of the mixtures was also important for the formation of these layers. The samples involving the medium size dendrimer (generation 4) and a slight excess of SDS (compared to the number of electric charges of the dendrimer) indicated low adsorption of surfactant that could be interesting for applications like the recovery of natural surfactants from raw oil-water mixtures. On the other hand, the smallest dendrimer (generation 2) delivered large numbers of molecules to the interface, which is appealing for applications such as biolubrication.

If one wishes to employ dendrimers as delivery vehicles of pharmaceuticals, they need to be transported in the body through cell membranes. The second part of this thesis examines the interactions between PAMAM dendrimers and negatively charged model biomembranes in the form of lipid bilayers. Amphiphilic polar lipids are the main constituents of these membranes, and some lipids are negatively charged. Bilayers act as barriers to protect the cell interior from the external environment. Biomembranes also contain a variety of other molecules such as cholesterol and proteins which make them very complicated systems. Two simple ways to study them is to use model lipid bilayers either supported on a silica surface or located in between two water droplets in oil. The results show that PAMAM dendrimers of generation 4 cross the negatively charged bilayers due to the electrostatic attraction between them and as a consequence the bilayers become more permeable. Thus, this process could perhaps allow other unwanted and even toxic molecules to enter. A key observation is that changing the strength of the electrostatic attraction between the dendrimer and the lipids could be an alternative method to reduce this toxic effect.

The last part of this work focuses on the development of alternative vehicles to transport nucleic acids made by the association of PAMAM dendrimers with negatively charged nucleolipids. Nucleolipids are derivatives of polar lipids that contain a nucleotide, the fundamental unit of DNA and RNA, in the head group. Layers formed by mixtures of dendrimers and nucleolipids have the potential to recognize selectively DNA and RNA, and some molecular recognition in these mixtures was demonstrated. These layers could also be employed as biosensors which are useful for analysis required for tissue matching and within forensic chemistry.

This thesis goes some way to outlining the sheer variety of implications of the interactions between dendrimers and small amphiphiles at surfaces. Many parameters, e.g. the dendrimer generation, the composition of the solution and the type of interface, are relevant for the tuning of the interactions. Besides the potential of dendrimers for use in the applications pointed out, these studies also allow the broadening and deepening of our knowledge of fundamental colloidal science. Through the comparison of these findings to the behavior of less well-defined branched polymers which are in more common use, considerably insight was gained into ways of improving their performance.



Popular Abstract in Swedish

I vår vardag stöter vi på många produkter, t ex. tvättmedel, läkemedel, livsmedel, schampo och färg med mera, vars funktioner är beroende av blandningar av polymerer och små amfifila molekyler i vatten. Polymerer är stora molekyler som byggts upp av mindre repeterande enheter som är sammanlänkade. Amfifila molekyler är uppbyggda av en vattenälskande (hydrofil) del och en vattenskyende (hydrofob) del. Kombinationer av polymerer och tensider används ofta för att ge ovan nämnda produkter önskad funktion och kontrollera blandningens stabilitet.

En typ av polymerer som rönt stor uppmärksamhet är så kallade dendrimerer. De har en speciell utformning och består av en kärna med ett väldefinierat antal grenar vilka är symmetriskt ordnade i en struktur som liknar en trädkrona. Syntesen av dessa molekyler sker i en serie steg där en ny generation bildas i varje steg, vilket betyder att ett visst antal nya grenar adderas och molekylens storlek ökar. De kemiska grupperna i grenarnas ändar kan varieras och på så vis ge olika typer av funktionalitet. De kan t ex. göras laddade för att attrahera molekyler av motsatt laddning.

Dendrimerernas grenade struktur är av betydelse eftersom grenarnas täthet är större vid ytan än nära kärnan. Denna egenskap medför att mindre molekyler, t ex. läkemedelssubstanser, kan kapslas in i dendrimerernas inre för att sedan levereras till ett specifikt mål i kroppen. En annan viktig medicinsk tillämpning är att med hjälp av dendrimerer kompaktera och föra DNA in i kroppen vilket kan användas för behandling av genetiska sjukdomar (även känt som genterapi).

Målet med denna avhandling var att undersöka växelverkan mellan dendrimerer med positiv laddning och små amfifila molekyler med negativ laddning. Dessa blandningar studerades med avseende på deras egenskaper vid gränsytor mellan fasta material och vatten, samt mellan luft och vatten, av två huvudsakliga skäl: (i) Funktionen av de tidigare nämnda produkterna beror till stor del på hur polymerer och amfifiler uppför sig i gränsytor samt (ii) teknikerna som används för att karaktärisera ytorna är väldigt känsliga och ger specifik information om struktur och komposition. Dendrimererna som används i detta arbete är poly(amidoamin) dendrimerer (PAMAM-dendrimerer) som kan sägas vara en av de mest allsidiga dendrimertyperna som syntetiserats hittills. Tre olika storlekar av dendrimerer, av generation 2, 4 och 8, har studerats här.

Den första delen av avhandlingen behandlar växelverkan mellan PAMAM-dendrimerer och den negativt laddade tensiden natriumdodecylsulfat (SDS). En tensid är en typ av amfifil molekyl och dess engelska namn ”surfactant” återspeglar dess egenskap att adsorbera vid gränsytor (surfactant = surface active agent, ytaktivt ämne). SDS är en av de vanligaste tensiderna i olika kommersiella produkter så som diskmedel och schampo. Blandningarna studerades vid gränsytorna kiseldioxid-vatten samt luft-vatten och resultaten relaterades till beteendet i bulklösning. Kiseldioxidytorna var, under gällande experimentella förhållanden, negativt laddade vilket gjorde att dendrimerer adsorberades till ytorna medan tensider repellerades. Resultaten visade att dendrimergeneration, bulk-sammansättning (eller dendrimer/tensid-kvoten) samt det sätt på vilket komponenterna blandades kunde varieras för att kontrollera struktur och sammansättning av de adsorberade lagren på den fasta ytan. Detta är intressant för utveckling av tillämpningar som molekylära sensorer eller för inkapsling av små molekyler, som t ex. färgmarkörer, vid gränsytor.

I luft-vattengränsytan adsorberade den rena tensiden till gränsytan men inte dendrimeren. I blandningar var adsorptionen störst för blandningar som innehöll den minsta dendrimeren (generation 2). En annan viktig faktor för bildandet av dessa yt-filmer var bulk-kompositionen i lösningen. De prover som innehöll dendrimerer av generation 4 samt ett litet överskott tensid (jämfört med antalet laddningar från dendrimerna) gav en mycket liten adsorberad mängd i gränsytan, vilket kan vara av intresse inom tillämpningar såsom urlakning av naturliga tensider från blandningar av råolja och vatten. Å andra sidan gav små dendrimerer av generation 2 en stor mängd material i gränsytan vilket kan vara attraktivt inom smörjmedel i medicinska tillämpningar.

Om dendrimerer ska användas som bärare av läkemedelssubstanser är det nödvändigt att de kan transporteras i kroppen och genom cellmembranen. Den andra delen av avhandlingen behandlar interaktionen mellan PAMAM-dendrimerer och anjoniska modellmembran. Polära lipider (en typ av amfifila molekyler), varav vissa är negativt laddade, är den huvudsakliga beståndsdelen i dessa membran i form av bilager. Dessa bilager verkar som barriärer för att skydda cellens inre från den omkringliggande miljön. Verkliga biomembran innehåller en mängd andra molekyler som kolesterol och proteiner vilket gör dem väldigt komplexa och utmanande att studera. Två enkla sätt att undersöka dem är att använda modeller bestående av lipid-bilager antingen adsorberade på en kiseldioxidyta eller lokaliserade mellan två vattendroppar i olja. Resultaten visar att katjoniska PAMAM-dendrimerer av generation 4 penetrerar anjoniska bilager på grund av elektrostatisk attraktion, vilket i sin tur gör bilagren mer genomträngliga. På så vis kan kanske även oönskade, eller till och med giftiga, molekyler passera membranet och tränga in i cellen. En nyckelobservation är att en minskning av den elektrostatiska attraktionen mellan dendrimerer och lipider kan vara ett alternativ för att reducera den toxiska effekten.

Den sista delen av arbetet fokuserar på utveckling av alternativa metoder för att transportera nukleinsyror med komplex bildade av PAMAM-dendrimerer och negativt laddade nukleolipider. Nukleolipider är varianter av lipider som innehåller en nukleotid, en grundläggande enhet i DNA och RNA, i huvudgruppen. Filmer som bildats av blandningar av dendrimerer och nukleolipider har potential att selektivt känna igen DNA och RNA. Dessa filmer kan också användas som biosensorer med användning inom vävnadsmatchning och rättskemi.

Denna avhandling visar på konsekvenserna av interaktioner mellan dendrimerer och amfifiler vid gränsytor. Många parametrar, såsom dendrimergeneration, lösningens sammansättning och typen av gränsyta, är av betydelse för att styra dessa interaktioner. Förutom att visa på potentialen för användning av dendrimerer inom de tillämpningar som nämnts så har den här studien även bidragit till att öka kunskapen inom fundamental yt- och kolloidkemi. Genom att jämföra resultaten från denna avhandling med beteendet hos mindre väldefinierade, men mer vanligt förekommande, grenade polymerer kan man också förbättra prestandan av de senare. (Less)
Abstract
The research described in this thesis aims to understand the interactions between cationic poly(amidoamine) (PAMAM) dendrimers and small oppositely charged amphiphiles at the solid-liquid and air-liquid interfaces in relation to the bulk solution behavior. There is high interest in PAMAM dendrimers because they are well-defined polymers with a hierarchical architecture which makes them promising materials as nanocapsules and gene vectors.

In the first part of the work, the bulk solution and interfacial properties of mixtures of PAMAM dendrimers of generations 2, 4 and 8 and the anionic surfactant sodium dodecyl sulfate (SDS) were studied. At the solid-liquid interface, the structure and composition of the adsorbed layers depend on... (More)
The research described in this thesis aims to understand the interactions between cationic poly(amidoamine) (PAMAM) dendrimers and small oppositely charged amphiphiles at the solid-liquid and air-liquid interfaces in relation to the bulk solution behavior. There is high interest in PAMAM dendrimers because they are well-defined polymers with a hierarchical architecture which makes them promising materials as nanocapsules and gene vectors.

In the first part of the work, the bulk solution and interfacial properties of mixtures of PAMAM dendrimers of generations 2, 4 and 8 and the anionic surfactant sodium dodecyl sulfate (SDS) were studied. At the solid-liquid interface, the structure and composition of the adsorbed layers depend on the dendrimer generation, the bulk composition and the pathway of adsorption. At the air-water interface, there is a synergistic enhancement of adsorbed surfactant in the presence of PAMAM dendrimers and the interfacial behavior depends on the non-equilibrium properties of the aggregates formed in the bulk solution. The implications of the interfacial properties of the layers formed by PAMAM/SDS mixtures are discussed with respect to their possible applications.

The interactions of PAMAM dendrimers and negatively charged lipid bilayers were also investigated. The aim was to understand the transport mechanism of dendrimers across anionic model biomembranes. The addition of PAMAM dendrimers of generation 4 to solid supported and droplet interface bilayers showed that the dendrimer makes the membranes more permeable and this allows them to translocate through the membranes. The results are employed to evaluate the use of PAMAM dendrimers as delivery vehicles.

The last section is dedicated to the examination of the interactions between PAMAM dendrimers of generation 4 and the nucleolipids dilauroylphospholiponucleosides based on adenosine (DLPA) and uridine (DLPU) at the silica-water interface. The aim was to develop ‘smart’ complexes on surfaces to achieve selective binding of nucleic acids. The layer structure and functionality depend on the method of adsorption and the type of nucleolipid. Only PAMAM/DLPA layers showed selective hydrophobic and hydrogen bonding base pairing interactions with different strands of nucleic acids through the formation of nucleolipid/nucleic acid multilayers. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Zauscher, Stefan, Duke University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
PAMAM, Surfactant, SDS, Lipid, Bilayer, Model Biomembrane, Nucleolipid, DLPA, DLPU, DNA, RNA, Neutron Reflectometry, Poly(amidoamine), Interface, Adsorption, Polyelectrolyte
pages
248 pages
publisher
Division of Physical Chemistry, Faculty of Science, Lund University
defense location
Lecture hall B, Center for Chemistry and Chemical Engineering, Lund
defense date
2014-09-26 10:15
ISBN
978-91-7422-364-4
language
English
LU publication?
yes
id
bcfe9397-4496-4b94-b097-b66777040c97 (old id 4616078)
date added to LUP
2014-09-03 13:25:18
date last changed
2016-09-19 08:45:02
@phdthesis{bcfe9397-4496-4b94-b097-b66777040c97,
  abstract     = {The research described in this thesis aims to understand the interactions between cationic poly(amidoamine) (PAMAM) dendrimers and small oppositely charged amphiphiles at the solid-liquid and air-liquid interfaces in relation to the bulk solution behavior. There is high interest in PAMAM dendrimers because they are well-defined polymers with a hierarchical architecture which makes them promising materials as nanocapsules and gene vectors.<br/><br>
In the first part of the work, the bulk solution and interfacial properties of mixtures of PAMAM dendrimers of generations 2, 4 and 8 and the anionic surfactant sodium dodecyl sulfate (SDS) were studied. At the solid-liquid interface, the structure and composition of the adsorbed layers depend on the dendrimer generation, the bulk composition and the pathway of adsorption. At the air-water interface, there is a synergistic enhancement of adsorbed surfactant in the presence of PAMAM dendrimers and the interfacial behavior depends on the non-equilibrium properties of the aggregates formed in the bulk solution. The implications of the interfacial properties of the layers formed by PAMAM/SDS mixtures are discussed with respect to their possible applications.<br/><br>
The interactions of PAMAM dendrimers and negatively charged lipid bilayers were also investigated. The aim was to understand the transport mechanism of dendrimers across anionic model biomembranes. The addition of PAMAM dendrimers of generation 4 to solid supported and droplet interface bilayers showed that the dendrimer makes the membranes more permeable and this allows them to translocate through the membranes. The results are employed to evaluate the use of PAMAM dendrimers as delivery vehicles.<br/><br>
The last section is dedicated to the examination of the interactions between PAMAM dendrimers of generation 4 and the nucleolipids dilauroylphospholiponucleosides based on adenosine (DLPA) and uridine (DLPU) at the silica-water interface. The aim was to develop ‘smart’ complexes on surfaces to achieve selective binding of nucleic acids. The layer structure and functionality depend on the method of adsorption and the type of nucleolipid. Only PAMAM/DLPA layers showed selective hydrophobic and hydrogen bonding base pairing interactions with different strands of nucleic acids through the formation of nucleolipid/nucleic acid multilayers.},
  author       = {Yanez, Marianna},
  isbn         = {978-91-7422-364-4},
  keyword      = {PAMAM,Surfactant,SDS,Lipid,Bilayer,Model Biomembrane,Nucleolipid,DLPA,DLPU,DNA,RNA,Neutron Reflectometry,Poly(amidoamine),Interface,Adsorption,Polyelectrolyte},
  language     = {eng},
  pages        = {248},
  publisher    = {Division of Physical Chemistry, Faculty of Science, Lund University},
  school       = {Lund University},
  title        = {Nanostructured surfaces created by the interactions of dendrimers and oppositely charged amphiphiles},
  year         = {2014},
}