**Po-Yen Chen 1, Wei-Chia Lee 1,\*, Hung-Jen Wang 1,2 and Yao-Chi Chuang 1,2**


Received: 20 December 2019; Accepted: 21 January 2020; Published: 23 January 2020

**Abstract:** Cystoscopic onabotulinumtoxinA (onaBoNTA) intradetrusor injection is an efficient and durable modality for treating sensory bladder disorders. However, the inconvenience of using the cystoscopic technique and anesthesia, and the adverse effects of direct needle injection (e.g., haematuria, pain, and infections) have motivated researchers and clinicians to develop diverse injection-free procedures to improve accessibility and prevent adverse effects. However, determining suitable approaches to transfer onaBoNTA, a large molecular and hydrophilic protein, through the impermeable urothelium to reach therapeutic efficacy remains an unmet medical need. Researchers have provided potential solutions in three categories: To disrupt the barrier of the urothelium (e.g., protamine sulfate), to increase the permeability of the urothelium (e.g., electromotive drug delivery and low-energy shock wave), and to create a carrier for transportation (e.g., liposomes, thermosensitive hydrogel, and hyaluronan-phosphatidylethanolamine). Thus far, most of these novel administration techniques have not been well established in their long-term efficacy; therefore, additional clinical trials are warranted to validate the therapeutic efficacy and durability of these techniques. Finally, researchers may make progress with new combinations or biomaterials to change clinical practices in the future.

**Keywords:** drug delivery; interstitial cystitis; onabotulinumtoxinA; overactive bladder; painful bladder syndrome

**Key Contribution:** This review examines the studies of injection-free onaBoNTA delivery for the treatment of sensory bladder disorders.
