DANA M. ASAD

PHARMACOLOGICAL EVALUATION OF
MICROEMULSION
CONTAINING BUTYLATED CHITOSAN AS
PROTEIN DELIVERY SYSTEM IN ANIMALS
BY
DANA M. ASAD
A thesis submitted in
Partial Fulfillment of the
Requirement for the Degree of
Master of Science
in Pharmaceutical Sciences
At
Petra University
Faculty of Pharmacy
Arnman, Jordan
March 2010
PHARMACOLOGICAL EVALUATION OF
MICROEMULSION
CONTAINING BUTYLATED CHITOSAN AS
PROTEIN DELIVERY SYSTEM IN ANIMALS
By
DANA M. ASAD
A thesis submitted in partial fulfillment of the requirement for the
Degree
of
Master of Sciences
At
Petra University
Faculty of Pharmacy
Amman, Jordan
March 2010
Supervisor
Name
Prof. Tawfiq Alhussainy
Co-suneryisor
Name
Dr. Nidal Qinna
Examination Committee
Name
Prof. Tawfiq Alhussainy
Dr. Nidal Qinna
Prof. Zuhair Muhi- Eldeen
Dr. Ghassan Shattat
Abstract
Over years, many ongoing investigations have been done to improve the oral
bioavailability of peptide and protein formulations. For insulin, many physical, chemical
and other barriers have been faced that needs to be overcome to deliver insulin orally and
increase its bioavailability and absorption. Low molecular weight chitosan has been
shown to be a potential carrier in delivering insulin; moreover, the mucoadhesive and
permeation enhancing properties of such polymer have been implanted to help in crossing
the biological barriers. Further modifications of the low molecular weight chitosan have
been studied over the last few years in order to produce more chitosan derivatives. In this
study the butylation process of different low molecular weight chitosans (1.3, 13 and
30kDa) and their effect on the enhancement of the molecule characteristics have been
investigated.
It was found that the low molecular weight butylated chitosans have interesting
characteristics over that of the chitosan such as the solubility enhancement and the
surface activity of the molecule and above all, the size of the nanoparticles obtained. In
vivo studies revealed that the molecular weight as well as the particle size of the insulinbutylated
chitosan affected the insulin bioavailability and pharmacological effect. The
low molecular weight and particle size of insulin butylated chitosan demonstrated
significant enhancement of the hypoglycemic effect of oral insulin when studied on
streptozotocin diabetic rat's model.
II
In conclusion, this study illustrated the effect of butylated chitosan as a chitosan
derivative on enhancing oral protein delivery using insulin as a protein model. This study
also highlights the importance of optimizing the molecular weight of the investigated
polymer along with determining the optimum particle sizc of the prepared formulation
intended to be administered orally.
m
Acknowledsements
It is difficult to thank everybody that helped me over the last 2 years to pass through the
difficult times of the examinations and the preparation of this work.
I would like first to thank my advisor Prof. Tawfiq Alhussainy, who was there for me in
every step of the way with his guidance, help and experience throughout this work and
am extremely grateful for everything he taught me. A lot of thanks goes to Dr. Nidal
Qinna, for his support, help and encouragement and above of everything the skills that he
helped me to develop throughout this work.
My greatest thanks go also to Dr. Adnan Badwan for his support, suggestions, and
discussions through this work. And to the JPM family for all the skills and techniques
they took the time to teach me, especially Eng. Nawzat Al-Jbour, who was there for me
in all the hard times and teached me a lot through this work. Also I would like to thank
Dr. Mayyas Remawi for his supervision and help.
I would also like to express my thanks to the committee members represented by Prof.
Tawfiq Alhussainy, Dr. Nidal Qinna, Prof. Zuhair Muhi- Eldeen and Dr. Ghassan shattat
for their valuable suggestions and comments that I will treasure for ever and remember
through my future plans.
IV
My deepest appreciation and thanks to my family who supported and believed in me, my
parents Mohammad and Eman Al Barghouthi who gave me great deal of supporg my
brothers Haz.em and Omar for being always there for me, and also my sister Zein for her
bright ideas and positive attitude that helped through the worst times.