Mixed Block Copolymer Solutions: Self-Assembly and Interactions

Abstract

This thesis incorporates studies on the aqueous systems of two types of thermoresponsive amphiphilic block copolymers; a series of nonionic triblock copolymers comprising blocks of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) denoted as PEO-PPO-PEO block copolymers, and a series of ionic diblock copolymers consisting of one charged block and one block of poly(N-isopropylacrylamide) (PNIPAAM). Various techniques, such as dynamic and static light scattering (DLS and SLS), small angle X-ray and neutron scattering (SAXS and SANS), high sensitivity differential scanning calorimetry (HSDSC), turbidimetry, electrophoretic mobility measurements, and two-dimensional proton NMR nuclear Overhauser effect spectroscopy (2D 1H NMR NOESY), were applied to study these block copolymer systems.

In the first part of the thesis, the influence of a bile salt, sodium glycodeoxycholate (NaGDC), on the self-assembly of the three PEO-PPO-PEO block copolymers, P123, F127 and P65, was studied. Apart from the fundamental physio-chemical point of view, the overall aim of this study was to investigate if these types of block copolymers are potential candidates to be used as bile acid sequestrants in the treatment of bile acid diarrhea and hypercholesterolemia diseases. It was found that the NaGDC does influence the self-assembly of these block copolymers in a similar way, but not as effectively as the classical ionic surfactants. At low bile salt concentrations and above the CMT of the pure aqueous solutions of these polymers, charged PEO-PPO-PEO micelle-NaGDC complexes are formed. The SAXS results indicated that the NaGDC molecules are located mostly in the corona of the block copolymer micelles, close to the core-corona interface. However, at higher bile salt concentrations, during their disintegration, these complexes are generally in coexistence with small NaGDC-rich complexes. The latter complexes resemble the NaGDC micelles in terms of size and structure. Among the three studied block copolymers, P65 micelles are the easiest to disintegrate by NaGDC. The F127 and P123 micelles show almost the same stability when interacting with NaGDC.

The second part in this thesis primarily describes the investigation of the effects of temperature, salt, PNIPAAM block length, and polymer concentration on the association behavior of a series of the three diblock copolymers, poly(N-isopropylacrylamide)-b-poly((3-acrylamidopropyl) trimethylammonium chloride) (PNIPAAMn-b-PAMPTMA(+)20), where n=24, 48, and 65. It was shown that the cloud point (CP) of the polymer solutions decreases upon an increase in PNIPAAM block length, and polymer and salt concentrations. At temperatures below CP of the polymer solutions, unimers and micellar/intermicellar clusters coexist. However, at temperatures above the CP, the dominant particles in the solutions are the large aggregates, which generally retain stable sizes in the presence of salt and upon increasing the temperature.

Finally the aqueous mixed solutions of PNIPAAM26-b-PAMPTMA(+)15 and poly(N-isopropylacrylamide)-b-poly(sodium 2-acrylamido-2-methyl-1-propanesulfonate) (PNIPAAM27-b-PAMPS(−)15) with an equimolar charge condition were studied. Mixed micelles were observed at total concentrations ranging from 0.2 to 0.5 wt % in all studied temperatures (10– 30 oC). The mixed micelles have a cylindrical structure, and are formed via an attractive electrostatic interaction between the oppositely charged PAMPTMA(+) and PAMPS(−) blocks. However, in addition to the charged blocks interaction, there is evidence of interaction between the PNIPAAM and the charged blocks, as demonstrated by 2D 1H NMR NOESY experiments.

Abstract (Swedish)

Popular Science Summary

Polymers are giant molecules consisting of a repetition of many small units (monomers) that are linked together by chemical bonds. If we consider a long necklace as a polymer chain, the beads are the monomers and the part of the thread which connects the beads together is the chemical bond. Polymers are important materials in our everyday life and they can be found e.g., in plastics, paints, fabrics, papers, food materials, cosmetics and drugs.
When a polymer is composed of more than one type of monomer, it is called a copolymer. Copolymers can have a variety of structures depending on how the different monomers are arranged in the polymer chain. One type of these copolymers is called block copolymers. For instance, if we attach the necklace with the pink beads (block A) to the end of the other necklace with the blue beads (block B), then this is called an A-B block copolymer or generally a ‘’diblock’’ copolymer. One can make A-B-A or A-B-C which are called ‘’triblock copolymers’’ or even block copolymers with more than three blocks.
Some of these block copolymers show interesting behavior when they are in contact with water. For instance, they may have a block that hates to be in contact with water (necklace with the red beads) and the other block which loves water (necklace with the blue beads). These types of block copolymers are scientifically called ‘’amphiphilic’’ block copolymers and they are considered polymeric surfactants. To have a favorable condition in water for both blocks, block copolymer chains may arrange themselves in a type of spherical structure that is called a ‘’micelle’’. In this micelle, the blocks which hate water, occupy the core to have less contact with water and the blocks which love water form the corona of the micelle. This spontaneous behavior of the amphiphilic block copolymers in water is called ‘’self-assembly’’ which happens above a specific polymer concentration. Some block copolymers are sensitive to a change in temperature, and hence, temperature can influence their self-assembly. These types of block copolymers are called ‘’thermoresponsive’’ block copolymers. Thus, they self-assemble or form micelles above a specific temperature.
Micelles of block copolymers play an important role in treatment of some specific diseases. These micelles, with sizes of about several tens of nanometers, can incorporate drug molecules and act as their carriers into the body. Due to their specific structure and the optimal size, they will not be removed from the blood stream and hence, the circulation time of the drug in the body could be increased. The physical and chemical characteristics of the block copolymer micelle can be tuned in a way that makes it suitable for targeting specific organs or tissues in the body to release the drug. Therefore it is very important to study the physical and chemical properties of the block copolymers and their self-assembly behavior. Meaning, for instance studying how different stimuli such as temperature, addition of acid, salt and other types of chemicals can effect on the self-assembly of these block copolymers.
This thesis contains studies on some of the amphiphilic and thermoresponsive diblock and triblock copolymers. Some of these block copolymers have already been used in pharmaceutical applications and some may have the potential to be used.
In this thesis it was demonstrated how block copolymer concentration, temperature, addition of salt and a natural body surfactant (bile salt) as well as the length of the loving-water or the hating-water blocks can influence the self-assembly of the micelles and break them up. Various techniques have been applied to study these block copolymer systems. Results demonstrated that some of these block copolymers could be potential candidates in the treatment of specific diseases for instance, hypercholesterolemia.

• author: Bayati, Solmaz
• supervisor: Karin Schillén; Tommy Nylander
• opponent: Professor Mortensen, Kell, Niels Bohr Institute, University of Copenhagen, Denmark
• organization: Physical Chemistry
• publishing date: 2016
• type: Thesis
• publication status: published
• subject: Physical Chemistry
• keywords: Polymer, Block Copolymer, PEO-PPO-PEO, Pluronics©, Bile Salt, NaGDC, PNIPAAM, PAMPTMA, PAMPS, Mixed Micelle, Self-Assembly, Mixed Complexes
• pages: 222 pages
• defense location: The Center for chemistry and chemical engineering, lecture hall B, Naturvetarvägen 14 (former Getingevägen 60), Lund
• defense date: 2016-06-15 10:30:00
• ISBN: 978-91-7422-450-4
• ISBN: 978-91-7422-459-7
• language: English
• LU publication?: yes
• id: 7ead6efe-3826-45df-a197-1a87eac0814f
• date added to LUP: 2016-05-19 14:34:29
• date last changed: 2018-11-21 21:23:51