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Peroral insulin delivery : new concepts and excipients

Sadeghi, A.M.M.

Citation

Sadeghi, A. M. M. (2008, December 10). Peroral insulin delivery : new concepts and excipients. Retrieved from https://hdl.handle.net/1887/13343

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/13343

Note: To cite this publication please use the final published version (if applicable).

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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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191 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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192 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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194

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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