ABSTRACTIn recent years, the application of microparticles in different fields including cosmetics, agriculture, pharmaceutics and biomedicine has been widely investigated.In this project, we aimed to improve the preparative methods for chitosan-triphosphate microparticles (Cs/TPP) for perspective application in the fields of cell encapsulation and controlled drug delivery. Prior to the preparation of chitosan-based microparticles, in order to confirm good biocompatibility and reproducibility, protocols have been established for the purification and characterisation of chitosan including the assessment of average molecular weight, protein content and degree of deacetylation.This study then primarily focused on the use of β-glycerophosphate (βGP) as an excipient, which is known to solubilize chitosan at neutral pH, thus allowing the preparation of chitosan microparticles (microspheres and toroidal) via ionotropic gelation under physiological conditions. The preparation of Cs-βGP/TPP microparticles was optimized varying several key process variables (concentration, flow rate, and frequency) and these microparticles were produced with a narrow size distribution (400 - 500 micro metre, spherical shape) and compared to Cs/TPP controls. The main result was the possibility to perform this process at neutral pH, although we have also demonstrated an improved toughness and cross-linking density of these microspheres as a result of the presence of β-glycerophosphate. Further, we have investigated the application of this method to a toroidal geometry, which provides advantages in terms of better transfer of oxygen and nutrients to any encapsulated materials. Cs/TPP and Cs-βGP/TPP 'micro-doughnuts' were also prepared and characterised. This research highlighted the evidence of a higher cross-linking density of these microparticles in comparsion with the spherical ones. In order to optimise the physicochemical characteristics of these microparticles for future applications as biomaterials, the surface of Cs/TPP and Cs-βGP/TPP microparticles was modified through an additional polyelectrolyte complexation with poly (sodium 4- styrene sulphonate) (PSS). The improved toughness and cross-linking density was confirmed by measuring the mechanical properties and solid content which indicated the successful complexation of PSS onto the surface of these microparticles.
|Date of Award||1 Aug 2013|
- The University of Manchester
|Supervisor||Nicola Tirelli (Supervisor) & Francesco Cellesi (Supervisor)|
- Chitosan, microspheres, B-glycerophosphate, ionotropic gelation.