Acknowledgements

It is not a fair task to acknowledge all the people who made this Ph.D.
thesis possible with a few words. However, I will try to do my best to
extend my great appreciation to everyone who helped me
scientifically and emotionally through out this study.

I shall begin with God the almighty: without His will I would have
never found the right path. His mercy was with me throughout my life
and ever more in this study. I thank Him for enlightening my soul
with the respected love and compassion for the other humans and
allowing me to enter a field where I could practice this desire.

With great appreciation I shall acknowledge all my colleagues at

Hakim Pharmaceutical Company, Tehran, Iran, who constantly
supported me throughout my Ph.D. In particular, I want to thank Dr.
Alimian, the general manager of the company, Dr. M. Parnianpour
and Dr. M.M.Sadeghi, members of the board of directors, for all their
support and encouragements. I, specially thank my dear co-workers
Dr. L. Majidi, Dr. S. Abedini, Dr. Jabalameli, Dr. M. Jenabi, Dr. S.
Asadi, Ms. Shafiee, Ms. Manafi and Mr. Pouladzadeh for putting up
with me during my Ph.D. period and always giving me words of
encouragement. I also thank Mr. Soloukaneh for his wonderful skill
in HPLC techniques. My special appreciation goes to my very good
friends Dr. Navid Nateghian and Dr. Shahriyar Abashzadeh for all
their scientific help and support throughout this study. You guys were
always real pals!

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I thank Prof. M. Faghihi, the head of veterinary school, Tehran, Iran,
for his help with the ex vivo studies in rabbits. I greatly appreciate all
the hard work and the tremendous support of Dr. Ejtemai-Mehr and
Dr. Partoazar for their extensive help with the in vivo animal studies
at the department of pharmacology, Tehran University. This part
would not be possible without their help. I shall extend my special
thanks to the department of pharmaceutics and biopharmaceutics,
School of pharmacy, University of Geneva, Switzerland. In particular
I want to thank Dr. F. Delie and Dr. R. Gurny for all their kindness
and for accepting me in Geneva. Also I want to specially thank
Megali, Briggete, Simon, Sarah and Elizabeth for all their care and
support with the Caco-2 cell studies. I also want to extend my
appreciation to Prof. B. Larijani, the head of endocrinology
department of Shariati hospital for all his support with the insulin
analysis and providing me with the RIA kits.

I, thank Mr. M. Weinhold, from the Center for Environmental

Research and Technology, Department of Production Technology,
Recovery and Recycling, Bremen, Germany, for his help with the
molecular weight studies and the intrinsic viscosities of the
synthesized polymers.

Many thanks to Prof. Karin Hoogedoory for making the translation of

the English summary into the Dutch language.

My very special thanks go to my dearest, best friend and mentor Dr.

Reza Avadi. He was the one who taught me all the basics of

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pharmaceutics and encouraged me to further pursue with my studies
by doing a Ph.D. in this field. This work was not possible without his
constant support and scientific help. My dearest Reza, I do not know
how to extend my gratitude towards you. You were always there with
me through the toughest moments, you saw me laugh in the lab and
you saw me cry in my misery. Your friendly advice, your soothing
words and your big heart helped me face all the obstacles and
continue with my work. I will never forget your kindness.

I owe a special thanks to my family, my mom and dad, my brothers

Ali and Amir and my sister in laws Neda and Pouneh who supported
me and helped me throughout my life and during this study. I dedicate
this work to you all. Mom, dad I do not know how to thank you
enough for providing me with the opportunity to be where I am today.
I love you so much.

I also dedicate this Ph.D. thesis to my two lovely children, Nikki and
Nima who are the pride and joy of my life. I love you more than
anything and I appreciate all your patience and support during
mommy’s Ph.D. studies.

At last I do not know how to begin with saying thank you to my soul
mate, my dearest husband and my best friend, Kamran. I love you for
everything, for being so understanding and for putting up with me
through the toughest moments of my life. I thank God for
enlightening my life with your presence. Sweet heart I love you! You
are the best thing that has ever happened to me.

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List of Publications

Scientific Articles

1. A.M.M.Sadeghi, M.Amini, M.R.Avadi, F.Seidi, M.Rafiee-

Tehrani, H.E. Junginger, Synthesis, characterization and
antibacterial effects of trimethylated and triethylated 6-NH2-6-
Deoxy Chitosan; J. Bioact. & Compat. Polym. 23(2008) 262-
275.

2. A.Bayat, A.M.M.Sadeghi, M.R.Avadi, M.Amini, M.Rafiee-

Tehrani, A .Shafiee, H.E.Junginger, J. Bioact. & Compat.
Polym. 21(2006) 433-444.

3. A.M.M.Sadeghi, F.A.Dorkoosh, M.R.Avadi, P.Saadat,

M.Rafiee-Tehrani, H.E. Junginger, Preparation,
characterization and antibacterial activities of chitosan, N-
trimethyl chitosan (TMC) and N- diethylmethyl chitosan
(DEMC) nanoparticles loaded with insulin using both the
ionotropic gelation and polyelectrolyte complexation methods,
Int. J. Pharm. 355(2008) 299-306.

4. A.M.M.Sadeghi, F.A.Dorkoosh, M.Weinhold, A.Bayat,

F.Delie, R.Gurny, M.B. Larijani, M.Rafiee-Tehrani, H.E.
Junginger, Permeation enhancer effect of chitosan and
chitosan derivatives: comparison of formulations as soluble
polymers and nanoparticulate systems on insulin absorption in
Caco-2 cells, Eur. J. Pharm. Biopharm 70(2008) 270-278.

5. A.M.M.Sadeghi, M.R.Avadi, Sh.Ejtemaimehr,

Sh.Abashzadeh, A.Partoazar, F.A.Dorkoosh, M.Faghihi, M.
Rafiee-Tehrani, H.E. Junginger, Development of a Gas
Empowered Drug Delivery system for peptide delivery in the
Small Intestine, J. Control. Rel. Article in press.

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A. Abstracts

A.M.M. Sadeghi, F.A. Dorkoosh, M.R. Avadi, A. Bayat, M.

Pouladzadeh, M. Rafiee-Tehrani, H.E. Junginger, One-step
synthesis of trimethyl chitosan (TMC) and its antibacterial
evaluation in comparison to chitosan and other alkylated
chitosan derivatives CRS (2006).

A.Bayat, A.M.M. Sadeghi, M.R. Avadi, R. Majlesi, M.

Amini, A. Shafiee, H.E.Junginger, M.R.Tehrani, Synthesis of
N-Dimethylethyl chitosan as a carrier for oral Delivery of
peptide Drugs CRS (2006).

A.M.M.Sadeghi, M.R. Avadi, F. Seidi, M. Rafiee-Tehrani,

H.E. Junginger Synthesis, characterization and antibacterial
effects of Triethylated 6-NH2-6-Deoxy Chitosan CRS Iran
(2007).

A.M.M.Sadeghi, F.A.Dorkoosh, A. Bayat, F. Delie, R.

Gurny, M.Rafiee-Tehrani, H.E. Junginger, Absorption of
insulin in vitro (Caco-2 cells) using chitosan and chitosan
derivatives both in nanoparticle form and free soluble solution
PSWC (2007).

A.M.M.Sadeghi, F. Seidi, M.R. Avadi, M. Rafiee-Tehrani,

H.E. Junginger Synthesis, characterization and antibacterial
effects of trimethylated 6-NH2-6-Deoxy Chitosan CRS (2007).

S. Abashzadeh, M.H.Hajimiri, A.M.M.Sadeghi, M.Rafiee-

Tehrani, R.Dinarvand, Monitoring of self assembly behavior
of chitosan derivatives in aqueous solution by photon
correlation spectroscopy CRS (2007).

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A.M.M.Sadeghi, F.A. Dorkoosh, M.R. Avadi, P. Saadat,
M. Rafiee-Tehrani, H.E. Junginger, Preparation and
characterization of N-Diethylmethyl chitosan (DEMC)
nanoparticles loaded with insulin using both the ionotropic
gelation and polyelectrolyte complexation methods IPORSIP
(2007).
A.M.M.Sadeghi, M. X. Weinhold, M.R. Avadi, M. Rafiee-
Tehrani, H.E. Junginger, Comparison of Molecular Weight,
Intrinsic Viscosity, Zeta Potential and Antibacterial Activities
of five alkylated Chitosan Derivatives CRS (2008).

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Curriculum Vitae
Assal M.M. Sadeghi was born on the 23rd of March of 1972 in Tehran, Iran.
She was awarded an Honours High School Diploma from Carson Graham
High School in Vancouver, Canada in 1990. She was accepted in the
Faculty of Science of the University of British Columbia (U.B.C.) where
she studied in the field of Microbiology and has conferred a degree of
Bachelors of Science in May of 1994. She was then accepted in the Faculty
of Graduate studies in the department of Pathology and Laboratory
Medicine, University of British Columbia for the Masters programme in
September of 1994. The title of her thesis was A Biological Mutant of
Coxsackievirus B3 and its Pathogenesis in Mice. She has taken the defence
examination on June of 1997 and obtained an A standing on the exam. She
has conferred the degree of Masters of Science in November of 1997. The
result of her study was published in the Journal of Virology in 2004.

She has then started to work at Hakim Pharmaceutical Company in Tehran,

Iran as a consultant in the department of Microbiology for 15 months. She
was then moved to the R&D department and worked as an assistant
manager on numerous projects. In September of 2006 she was also given
the title of project manager of the company where she had to closely follow
all the projects and parties involved in the company.

In December 2005, she was accepted as a Ph.D. researcher in Leiden

University, Leiden, The Netherlands. She has done most of her research in
Tehran, Iran under close supervision of her promoters Prof. H.E. Junginger
and Prof. M. Rafiee-Tehrani. She has presented her PhD project in the area
of peroral peptide delivery at Controlled release symposium (CRS) in July
2006 (Vienna, Austria), July 2007 (Long Beach, U.S.A.) and July 2008
(New York, U.S.A.); Pharmaceutical Sciences World Congress (PSWC)
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(Amsterdam, The Netherlands) in April of 2007; the 5th International
Postgraduate research symposium on pharmaceutics (IPORSIP) (Istanbul,
Turkey) in September of 2007; and the 6th world meeting on Pharmaceutics,
Biopharmaceutics and Pharmaceutical Technology (PBP) in Barcelona,
Spain April 2008. She was awarded with the best poster presentation in Sep
2007 at IPORSIP conference.

A patent for her studies in developing a novel peroral delivery system has
been filed by Lupin Company (Pune, India) in June 2008.

Assal M.M. Sadeghi will continue with her scientific carrier with Hakim
Pharm. Co. as part of a new research group on drug research and
development.

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