Colon Targeted Drug Delivery System Dissertation Abstract

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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.

Date
2014

Rights
The Author

Publisher
Massey University

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.

URI
http://hdl.handle.net/10179/5666

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