Enhancement of the drug efficacy and elimination of the side effects resulting from drug overdoses are an essential aspect in drug therapy. To achieve these demands two general guidelines have been used; producing new drugs with higher selectivity and therefore less side effects and improving controlled/sustained drug delivery agents based on polymers. Thus, the relationship between the active pharmaceutical ingredient and the polymeric system is important in the development of a drug delivery system and several considerations need to be taken in to account, for example the polymer should be biocompatible, biodegradable, and non-toxic and physiochemical properties. Because mucus is the first barrier with which food and drugs can interact with and diffuse through to be absorbed and enter the circulatory system, characterisation of mucin is an essential step towards establishing suitable pharmaceutical excipients. Therefore, the aim of the present study was to investigate the potential to construct and study drug delivery systems based on polysaccharides. The physicochemical characterisation of extensively degraded pig gastric mucin was studied and revealed that this type of mucin contains: protein, carbohydrate (Fuc, Gal, GalN, GlcN) and sialic acid, which provides the negative charges that becomes progressively stronger with increasing pH. The measurements of viscosity vs. shear rate showed that mucin has a shear thinning behaviour and a relatively low viscosity which is consistent with a high critical overlap concentration (c*), small hydrodynamic size and hence compact structure. The insight in to the compositional, hydrodynamic and viscoelastic properties support the understanding of mucin interactions with polysaccharide based drug delivery systems. Several polysaccharides including chitosan (Cs), two grade of alginates; high guluronate alginate (HGA) and low guluronate alginate (LGA) (which differ in structural conformation) and two kinds of pectin; high methoxyl pectin (HMP) and low methoxyl pectin (LMP) (with different degrees of esterification) have been characterised. The structure of these polysaccharides as powder have been studied; Fourier transform infrared spectroscopy ) findings indicate the structure and the function group for each polysaccharide whereas powder X-ray diffraction measurements displays that all the polysaccharide which were analysed are amorphous in nature except LMP which has a number of sharp crystalline peaks. In addition, solution properties of these polysaccharides such as zeta potential and intrinsic viscosity were investigated at several ionic strengths and pH. Furthermore the molecular weights were evaluated based on intrinsic viscosity and the Smidsrød-Haug stiffness parameter (B) and intrinsic persistence length (Lp) were estimated using the novel ionic strength dependency of zeta potential method and intrinsic viscosity (traditional method). The interaction between polysaccharides and pig gastric mucin were evaluated based on relative viscosity. It has been suggested that polysaccharide–mucin interactions are not only driven by electrostatic forces, but also by the molecular weight, conformation and flexibility of the polymer also played significant roles. As the mucin-HGA system displayed exceptionally high viscosity, the viscoelastic properties of this system were extensively studied. The mechanical spectra of the mucin-HGA blends indicate that with the exception of the system involving only HGA (0 % mucin) and 60 % mucin, all mixtures including mucin itself displayed typical ‘weak gel’ rheological behaviour and the gel became stronger with decreasing HGA content in the system. Moreover 80 % of mucin was successfully encapsulated within phospholipids bilayer using liposomal encapsulation technology. The liposomal vesicles with encapsulated mucin display larger sizes than the control vesicles (prepared in DI water) this may be due to the electrostatic interaction between mucin molecules and phospholipid which is the main component the vesicles. In the final part of the thesis the hydrogel containing chitosan and naturally occurring polyanions and its potential for drug release were studied. Chitosan - polyanion (HGA, LGA, HMP and LMP) hydrogels complexes were successfully prepared (in acetate buffer 0.05M, 4.3 pH) at various ratios (10 %, 30 %, 50 %, 70 % 90 % of Cs) using the ionotropic gelation method. The freeze dried hydrogels were characterized by FT-IR and XRD and the results confirmed the electrostatic interactions between chitosan and polyanions at all ratios and percentage yield of hydrogel ζ and ηsp results of the supernatant was determined and it was found that the optimum ratios 3:7 and 1:1 of chitosan-pectins and chitosan-alginates respectively. The hydrogels of ideal ratios were studied by determining zeta potential, particles size, water uptake, morphology by scanning electron microscopy for freeze dried hydrogels and optical microscopy analysis for homogenous suspension. In addition, dynamic small deformation oscillatory measurements and adhesion property were studied. Finally, ibuprofen was successfully encapsulated by the chitosan-polyanion hydrogel complexes and the encapsulation efficiency of the formulations was calculated. Finally the drug release behaviour of the formulations was in vitro assessed over the time. The findings demonstrated that HMP and LGA hydrogels displayed the highest percentage of retained ibuprofen followed by HGA and LMP. This could be attributed to the fibrous appearance small size of pores which may impedes movements of entrapped molecules.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:721485 |
| Date | January 2016 |
| Creators | Abodinar, Atiga Emhemed |
| Contributors | Morris, Gordon ; Smith, Alan |
| Publisher | University of Huddersfield |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.hud.ac.uk/id/eprint/32608/ |
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