Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Surgery

Supervisor

Sumit Dave

Abstract

Intra-detrusor Botulinum Toxin-A (BTX-A) injection is the gold standard treatment for detrusor overactivity in clinical practice when medical treatment fails. Despite satisfactory results of BTX-A injection, the endoscopic procedure still has risks of anaesthetic and operative complications. Several studies have investigated more simple ways to deliver BTX-A to the detrusor muscle but with limited success. In our study, we assessed the evidence of BTX-A delivery using a newly modulated hyaluronan-phosphatidylethanolamine (HA-PE) carrier in a rat model through BTX-A-HA-PE bladder instillations. We used histological evidence of SNAP-25 protein cleavage and detection of Alexa FluorÒ594-labelled BTX-A as a proof of physical BTX-A delivery across the urothelium. In addition, we assessed the functional impact of using HA-PE on rat detrusor muscle through urodynamic assessment both at baseline and 2 weeks later after 1% acetic acid instillation. We found positive histological evidence of SNAP-25 cleavage, detection of Alexa FluorÒ594-BTX-A red fluorescence in bladder tissue supporting that HA-PE may be an efficient carrier to deliver BTX-A across the urothelium.


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