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Title: Developing novel mucoadhesive chitosan based formulations for drug delivery to the urinary bladder
Author: Kolawole, Oluwadamilola Miriam
ISNI:       0000 0004 7966 8360
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2019
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My PhD project aims to develop novel chitosan derivatives (with superior mucoadhesiveness) for transmucosal application. The intravesical route was chosen as the exemplar transmucosal mode of drug delivery due to the limited therapeutic efficiency of conventional bladder cancer formulations. Drug carriers with improved mucoadhesive properties may prolong drug residence in the bladder. First, three chitosan grades were used to prepare chitosan/β-glycerophosphate in situ gelling mixtures and from these grades, the high molecular weight graded chitosan (HCHI) was chosen for chemical derivatisation based on its superior gelation, mucoadhesive and drug release potential. HCHI was conjugated with varying amounts of methacrylate or phenylboronate groups in order to evaluate the influence of the type and amount of conjugated hydrophobic pendant group on their physicochemical and mucoadhesive properties. The boronated and methacrylated chitosans were characterised using 1H NMR and FT- IR. There was good correlation in the extent of hydrophobic modification for methacrylated and boronated chitosans using 1H NMR and ninhydrin test. Methacrylated and boronated chitosan exhibited comparable resistance to pH influence on their solubility. The degree of methacrylate or boronate conjugation had a significant influence on the mucoadhesiveness of the drug carriers studied using a urine flow-through technique/fluorescent microscopy as well as a texture analyser, on porcine bladder in vitro. Boronate groups conferred superior mucoadhesive behaviour on chitosan relative to methacrylate groups. Methacrylated chitosan displayed a similar safety profile to the parent chitosan based on MTT assay on UMUC3 bladder cancer cells. The biocompatibility studies of boronated chitosan will be carried out in future studies using bladder cell lines despite the fact that several in vitro and in vivo studies have established the safety of phenylboronic molecules. Methacrylation and boronation of chitosan has been identified as efficient strategies to generate more mucoadhesive drug carriers which could prolong drug residence time in the bladder thereby improving therapeutic outcomes of bladder cancer patients. These novel polymers were easily synthesised requiring minimal equipment suitable for industrial scale-up. These excipients could be used to formulate affordable transmucosal dosage forms with superior mucoadhesiveness for a variety of biomedical applications.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral