Chitosan and carboxymethylcellulose functionalized graphene oxide as nanocarriers for chemotherapy of bladder cancer

• Main Author: Low, Ying Zhen
• Other Authors: Tan Lay Poh
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2021
• Subjects: Engineering::Materials; Engineering::Nanotechnology
• Online Access: https://hdl.handle.net/10356/149844
• Institution: Nanyang Technological University

Bladder cancer is the costliest cancer to treat due to its high recurrence rate which necessitates life-long monitoring. Intravesical treatment of bladder cancer involves instillation of therapeutic agent into the bladder cavity via a catheter, which enhances localized treatment concentration and efficacy, while reducing systemic absorption. However, this method introduces a different set of challenges, including drug dilution by urine, as well as non-permeability of the bladder wall. The use of drug delivery systems can potentially increase drug residence and permeability to achieve optimal therapeutic effects without compromising safety. This study therefore, proposes functionalized graphene oxide as bladder cancer targeting drug delivery system. Physical loading of chemotherapeutic drug, camptothecin on graphene oxide sheets retains chemical structures of drug with relatively high loading capacity. The functionalizing polymers, chitosan and carboxymethylcellulose, introduce dispersion stability, biocompatibility and mucoadhesive property to the otherwise ill-performing graphene oxide. The retention ability in ex-vivo porcine bladder demonstrated muco-adherence for up to 20 urine voiding, which is beyond the standard intravesical therapy with one voiding retention. In physiological conditions, the dispersion stability surpassed that of graphene oxide, especially in high protein and salt conditions of simulated disease urine. The drug loading capacities stood at the higher range among other reported bladder drug delivery systems while cytocompatibility study with L929 cell lines established a minimal decrease of cell viability for up to a concentration of 50µg/ml. Conclusively, both nanocarriers show promises as intravesical drug delivery systems for bladder cancer treatment, with chitosan functionalized graphene oxide prevailing over carboxymethylcellulose functionalized graphene oxide due to the greater stability in simulated disease environment and minimal alteration to the bladder mucosa surface.