Stimuli sensitive polysaccharide based hydrogels as colon targeted drug delivery vehicles : a thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry, Massey University, Turitea campus, Palmerston North, New Zealand
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Date
2014
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Massey University
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Abstract
Administering drugs orally is by far the most widely used route of administration that
will help eliminate the pain caused by injection, psychological barriers associated with
multiple daily injections and possible infection from injection sites. However, it is
important for oral drug administration to overcome several different obstacles during
the delivery through the gastrointestinal tract. The barriers can be morphological
barriers and physiological factors such as a wide range of pH and enzymatic activities.
The lower water content and fluid mobility of the colon, which leads to longer retention
times and also lower proteolytic activity of colon compared to other areas of the
gastrointestinal tract, make the colon an ideal site for both systemic and local delivery
of drugs. Therefore aggressive research efforts have recently focused on development of
new strategies for delivering drugs to the colon.
As a drug delivery systems, hydrogels have received increasing attention due to their
outstanding merits. Among the various hydrogels, including natural, synthetic and
natural/synthetic hybrid hydrogels, chitosan has attracted significant attention in a broad
range of pharmaceutical and biomedical applications. Chitosan is a hydrophilic
polyelectrolyte heteropolysaccharide composed of randomly (1→4)-linked 2-
acetamido-2-deoxy-β-D-glucopyranose and 2-amino-2-deoxy-β-D-glucopyranose
linked by (1→4)-β-glycosidic bonds. Unlike most known bioadhesive polymers,
chitosan displays unique pharmaceutical and biomedical applications due to the large
number of hydroxy and amino groups on the backbone of chitosan. These functional
groups can be readily modified. This study was commenced with the aim of engineering
a carrier with high enough physicochemical stability to reach the colon and to be able to
protect a drug from various obstacles throughout the gastrointestinal tract. In this study,
a new generation of chitosan derivatives was developed. Furthermore, their viability
was investigated for potential applications as drug carriers to the colon. Chitosan based
films with improved physical properties from introducing a cyclic imide moiety into the
chitosan matrices was developed and characterised. Mechanical, thermal and chemical
analyses of these films show that the heterocyclic imide linkage imparts excellent
thermal, mechanical and chemical stability to the chitosan film. Additionally, spray
dried chitosan microspheres with improved mechanical stability were examined for the
controlled drug release of bovine serum albumin as a model protein drug. Additionally,
a novel generation of amphoteric crosslinked chitosan derivatives was designed to be
pH sensitive and bacterially degradable. Tabletted carriers were designed to protect the
drug from the harsh acidic environment of the stomach and the rigorous enzymic
activity of the small intestine and deliver the drug to the colon. Tabletted formulation
forms of these novel amphoteric derivatives of chitosan showed the excellent potential
formulations as colon specific drug delivery vehicles.
Description
The following journal articles have been removed due to copyright restrictions:
Kavianinia, I.; Plieger, P. G.; Kandile, N. G.; Harding, D. R., Fixed-bed column
studies on a modified chitosan hydrogel for detoxification of aqueous solutions from
copper (II). Carbohydrate Polymers. 2012, 90 (2), 875–886;
Kavianinia, I.; Plieger, P. G.; Kandile, N. G.; Harding, D. R., New hydrogels based
on symmetrical aromatic anhydrides: Synthesis, characterization and metal ion
adsorption evaluation, Carbohydrate Polymers. 2012, 87 (1), 881–893;
Kavianinia, I.; Plieger, P. G.; Kandile, N. G.; Harding, D. R., In Vitro Evaluation of
Spray-Dried Chitosan Microspheres Crosslinked with Pyromellitic Dianhydride for Oral
Colon-Specific Delivery of Protein Drugs. Article first published online: 13 Feb 2013.
Keywords
Drug delivery systems, Drug adnimistration, Hydrogels, Chitosan, Colon