Amphiphilic block copolymers of poly(ethylene oxide) and poly(perfluorohexylethyl methacrylate): from synthesis to applications [Elektronische Ressource] / von Hazrat Hussain

Hazrat Hussain

Informations

• Publié par: martin-luther-universitat_halle-wittenberg
• Publié le: 01 janvier 2004
• Nombre de lectures: 12
• Langue: English
• Poids de l'ouvrage: 5 Mo

Extrait

Amphiphilic Block Copolymers of Poly(ethylene oxide) and
Poly(perfluorohexylethyl methacrylate): from Synthesis to
Applications

Dissertation
zur Erlangung des akademischen Grades
Doktor-Ingenieur (Dr. -Ing.)

genehmigt durch

Mathematisch-Naturwissenschaftlich-Technische Fakultät
(Ingenieurwissenschafticher Bereich)
der Martin-Luther-Universität Halle-Wittenberg

von Herrn M.Phil. Hazrat Hussain
geb. am 05.01.1973 in Nawan Killi (Pakistan)



Gutachter:

1. Prof. Dr. J. Kressler
2. Prof. Dr. K. Mäder
3. Prof. Dr. S. Förster

Halle (Saale), den 19-08-2004
urn:nbn:de:gbv:3-000007140
[http://nbn-resolving.de/urn/resolver.pl?urn=nbn%3Ade%3Agbv%3A3-000007140]






Dedicated to My Loving Parents









III
Acknowledgement

I would like to express my deep sense of gratitude, sincere thanks to my advisor Prof. Dr.
Jörg Kressler for his valuable suggestions, discussions, continued encouragement and
inspirations through out my stay here, and providing me an opportunity to work in his
group.
I am also obliged to Prof. Dr. R. Neubert (Halle), Prof. Dr. A. Blume (Halle),
Prof. Dr. H. J. Radusch (Halle), Dr. S. Höring (Halle), Dr. N. M. Nubarov (Moscow,
Russia), Dr. P. Phol (Berlin), Dr. R. Thomann (Freiburg), Dr. Y. Mrestani (Halle), Dr. A.
Kerth (Halle) Dr. M. Janich (Halle) and Dr. O. Kryolova (Berlin) for their help and
cooperation over the course of my work in their laboratories.
I am grateful to all colleagues, Dr. K. Busse, Dr. J. Vogel, Dr. H. Kausche, Dr. Z.
Funke, Dr. H. Budde, Dr. C. Schwinger, N. Mahmood, B. Borisova, C. Peetla, S. Kaiser,
for their cooperation and nice company during my stay.
Special thanks and appreciation are due to Dr. K. Busse and my former colleague
Dr. T. Menke not only for their fruitful discussions related to my research work, but also
for their help in solving my day to day problems which any student might face in a
foreign land.
I would like to acknowledge DFG and BMBF for financial support of this work.
Finally, I wish to pay my gratitude to my loving family members for their
encouragement throughout my studies.




M.Phil. Hazrat Hussain


IV
This dissertation is based on the following publications:

1. H. Hussain, K. Busse, A. Kerth, A. Blume, N. S. Melik-Nubarov, and J. Kressler
“Interaction of poly(ethylene oxide) and poly-(perfluorohexylethyl methacrylate)
containing block copolymers with biological systems” (submitted)

2. H. Hussain, A. Kerth, A. Blume, J. Kressler “Amphiphilic block copolymers of
poly(ethylene oxide) and poly(perfluorohexylethyl methacrylate) at the water
surface and their penetration into the lipid monolayer” J. Phys. Chem. B 2004,
108, 9962.

3. H. Hussain, A. Kerth, K. Busse, A. Blume, J. Kressler “Block copolymers in
contact with lipid monolayer” Polym. Mater. Sci. Engi.2004, 90, 563.

4. H. Hussain, K. Busse, J. Kressler, Poly(ethylene oxide) and
Poly(perfluorohexylethyl methacrylate) Containing Amphiphilic Block
Copolymers: Association Properties in Aqueous Solution” Macromol. Chem.
Phys. 2003, 204, 936.

5. H. Hussain, H. Budde, S. Höring, K. Busse, J. Kressler, “Synthesis and
characterization of poly(ethylene oxide) and poly(perfluorohexylethyl
methacrylate) containing triblock copolymers” Macromol. Chem. Phys. 2002,
203, 2103.

6. K. Busse, H. Hussain, H. Budde, S. Höring, J. Kressler, “Micelle formation of
perfluorinated triblock copolymers in water” Polym. Prep. 2002, 43, 366.

7. K. Busse, J. Kressler, H. Hussain, O. O. Krylova, P. Pohl, S. Höring, H. Budde,
“Behavior of amphiphilic block copolymers at model membranes” Polym. Mater.
Sci. Engi. 2001, 84, 100.

V
8. H. Hussain, C. Peetla, J. Kressler, N. M. Nubarov, P. Pohl, “Interaction of
amphiphilic block copolymers with model bilayer membranes and encapsulation
of a model hydrophobic drug by block copolymer micelles: potential
pharmaceutical applications” (to be submitted).
VI Contents

Contents

1. Introduction 1
1.1. Block copolymers 1
1.2. ers in solid state 2
1.3. Block copolymers in solution 6
1.4. Applications of block copolymers 11

2. Synthesis and characterization of bulk properties of poly(ethylene oxide) 14
and poly(perfluorohexylethyl methacrylate) containing block copolymers
2.1. Introduction 14
2.2. Experimental section 16
2.2.1. Materials 16
2.2.2. Synthesis by atom transfer radical polymerization 16
2.2.3. Experimental techniques 17
2.3. Results and discussion 20
2.3.1. Molecular characterization 20
2.3.2. Microphase separation in bulk 23
2.3.3. Effect of poly(perfluorohexylethyl methacrylate) block on 27
crystallinity and thermal properties of the block copolymers
2.4. Conclusion 34

3. Behavior of poly(ethylene oxide) and poly(perfluorohexylethyl metha- 36
crylate) containing block copolymers in aqueous solution
3.1. Introduction 36
3.2. Experimental section 39
3.2.1. Surface tension measurements 39
3.2.2. Dynamic light scattering 39
3.2.3. Transmission electron microscopy 40
3.3. Results and discussion 41
VII Contents
3.3.1. Micelle formation 41
3.3.2. Effect of concentration, temperature, ultrasonic treatment, 45
and time
3.3.3. Morphology of solvent evaporated samples 52
3.4. Conclusion 56

4. Amphiphilic block copolymers of poly(ethylene oxide) and poly(perfluoro- 57
hexylethyl methacrylate) on water surface and their penetration into lipid
monolayer
4.1. Introduction 57
4.2. Experimental section 60
4.2.1. Materials 60
4.2.2. Surface pressure measurements 60
4.2.3. Infrared reflection absorption spectroscopy setup 61
4.3. Results and discussion 63
4.3.1. Interfacial properties of the block copolymers 63
at the air/water interface
4.3.2. Penetration of lipid monolayer by block copolymer chains 67
4.3.3. Infrared reflection absorption spectroscopy investigations 70
4.4. Conclusion 78

5. Potential pharmaceutical applications of amphiphilic block copolymers of 80
poly(ethylene oxide) and poly(perfluorohexylethyl methacrylate) or
poly(n-decylmethacrylate)
5.1. Introduction 80
5.2. Experimental section 84
5.2.1. Cytotoxicity measurements 84
5.2.1.1. Purification of the copolymers 84
5.2.1.2. Cell culturing 84
5.2.2. Interaction of block copolymers with lipid bilayers 85
5.2.2.1. Planar bilayer membranes 85
VIII Contents
5.2.2.2. Liposomes 86
5.2.3. Encapsulation of a model hydrophobic drug by block 88
copolymer micelles
5.2.3.1. Preparation of drug loaded micelles 88
5.2.3.2. Quantitative evaluation of the encapsulated drug 90
content in dried micelles
5.2.3.3. Effect of freeze-thawing on drug loaded micelle 91
size distribution
5.3. Results and discussion 92
5.3.1. Cytotoxicity results 92
5.3.2. block copolymers in contact with lipid bilayers 93
5.3.2.1. Interaction with planar lipid bilayer 93
5.3.2.2. Interaction with liposomes 95
5.3.3. Encapsulation of testosterone undecanoate as model 98
hydrophobic drug by block copolymer micelles
5.4. Conclusion 104

6. Summary and perspectives 106
7. Zusamenfasung 113
Literature 119
Resume 131


IX Abbreviations and symbols
Abbreviations and symbols

PEO Poly(ethylene oxide)
PFMA Poly(perfluorohexylethyl methacrylate)
PDMA Poly(n-decylmethycrylate)
PE-b-PEE Poly(ethylene-b-ethylethylene)
PCL-b-PB Poly(ε-caprolactone-b-butadiene)
PEO-b-PBO Poly(ethylene oxide-b-butylene oxide)
PEO-b-PEE oxide-b-ethylethylene)
PEO-b-PEP Poly[(ethylene oxide)-b-(ethylene-alt-propylene)]
PEO-b-PHMA Poly(ethylene oxide-b-hexyl methacrylate)
PEO-b-PS oxide-b-styrene)
PMMA Poly(methyl methacrylate)
PPO Poly(propylene oxide)
ATRP Atom transfer radical polymerization
DPhPC 1, 2-Diphytanoyl-sn-glycero-3-phosphocholine
DPhPS 1,2-Diphytanoyl-sn-glycero-3-[phospho-L-serine]
THF Tetrahydrofuran
MeOH Methanol
DMF Dimethyl formamide
DMSO methly sulfoxide
KOH Potassium hydroxide
HEPES N-2-Hydroxyethylpiperazine-N'-2-ethanesulfonic acid
PMDETA Pentamethyldiethylene triamine
EDTA Eethylenediaminetetraacetic acid
MMT Met