Nano-BTA: A New Strategy for Intravesical Delivery of Botulinum Toxin A

Abstract

Botulinum neurotoxin subtype A (BoNT-A) has been part of the urology treatment arsenal since it was first used in the treatment of detrusor-sphincter dyssynergia more than 30 years ago. BoNT-A has been recommended as an effective treatment for neurogenic detrusor overactivity and overactive bladder. However, direct intradetrusor injection of BoNT-A using cystoscopy after anesthesia may cause hematuria, pain, and infection; these adverse events have motivated urologists to find less invasive and more convenient ways to administer BoNT-A. The development of nanotechnology has led to the advancement of intravesical drug delivery. Using versatile nanocarriers to transport BoNT-A across the impermeable urothelium is a promising therapeutic option. In this review, we discuss the effectiveness and feasibility of liposomes, thermosensitive polymeric hydrogels, and hyaluronan-phosphatidylethanolamine as carriers of BoNT-A for intravesical instillation. To date, these carriers have not reached a similar efficacy as intradetrusor injections in long-term observations. Hopefully, researchers will make a breakthrough with new nanomaterials to develop clinical applications in the future.

A comprehensive review on hydrogel materials in urology: Problems, methods, and new opportunities

“…Clinical studies conducted by the team of Jan Krhut et al demonstrate that TC‐3 hydrogel can also be used for intravesical delivery of botulinum toxin A (OnabotA) during the treatment of idiopathic overactive bladder. Intravesical infusion of the hydrogel has been shown to reduce urinary urgency and eliminate symptoms of overactive bladder 76–78 . Hydrogel mucoadhesive systems anchor to the urinary bladder wall thanks to the occurrence of interactions such as physical entanglement, hydrophobic interactions, hydrogen bonds, electrostatic interactions, the presence of covalent bonds, and the effect of external forces, for example, magnetic field 73 .…”

“…Intravesical infusion of the hydrogel has been shown to reduce urinary urgency and eliminate symptoms of overactive bladder. [76][77][78] Hydrogel mucoadhesive systems anchor to the urinary bladder wall thanks to the occurrence of interactions such as physical entanglement, hydrophobic interactions, hydrogen bonds, electrostatic interactions, the presence of covalent bonds, and the effect of external forces, for example, magnetic field. 73 However, the high viscosity of the hydrogel attached to the urinary bladder walls can often cause significant irritation of the bladder epithelium, resulting in the formation of blood clots and inflammatory reactions.…”

“…The team of Jan Krhut et al [76][77][78] Thermosensitive TC-3 hydrogel Botulinum toxin A (OnabotA) Clinical trials…”