Past, Present and Future of Chemodenervation with Botulinum Toxin in the Treatment of Overactive Bladder

Abstract

Purpose We systematically reviewed both pre-clinical and clinical studies on bladder chemodenervation with onabotulinumtoxin A to highlight current limitations and future drug delivery approaches. Materials and Methods We identified peer-reviewed basic and clinical research studies of onabotulinumtoxin A (onaBoNT-A) in the treatment of neurogenic bladder and refractory idiopathic overactive bladder (OAB) published between March 2000 and March 2016. Paired investigators independently screened 125 English language articles to identify controlled studies on onaBoNT-A administration in MEDLINE® database and abstracts presented at annual American Urological Association meetings. The review yielded an evidence base of over 50 articles relevant to the approach of injection free onaBoNT-A chemodenervation. Results The efficacy and safety of intradetrusor injection of onaBoNT-A for the treatment of OAB is sensitive to both injection volume and depth, and this issue has motivated researchers to study injection-free modes of drug delivery into the bladder. Urothelial denudation with protamine sulfate or dimethyl sulfoxide (DMSO), liposome encapsulated onaBoNT-A, and other physical approaches are all being studied to increase toxin permeability and avoid intradetrusor injections. Liposome encapsulated onaBoNT-A enhances toxin activity while reducing its toxin degradation. The safety and efficacy of liposome encapsulated onaBoNT-A was tested in a multi-center, placebo controlled study. Although this treatment successfully reduced urinary frequency and urgency, it did not significantly reduce urgency urinary incontinence episodes. Conclusions Intradetrusor injection of onaBoNT-A is safe and effective as reported in several large multicenter randomized controlled trials. Injection of the toxin into the bladder wall impairs both afferent and efferent nerves, but drug delivery approaches that avoid injections impair only bladder afferent nerves. Further studies are needed to develop better drug delivery platforms that overcome the drawbacks of intradetrusor injection, increase patient acceptance, and reduce the treatment costs.

Current management of refractory overactive bladder

“…The severity of frequency and urgency decreased; however, the urine retention rate and urge incontinence rates were not changed. This suggests that intravesical instillation of liposome‐encapsulated BoNT‐A can impair afferent nerves but not efferent nerves …”

Development and Evaluation of a (SEDDS) Self - Emulsifying Drug Delivery System for Darifenacin Hydrobromide

“…As such, a droplet of smaller size has larger surface area of interface for drug absorption. 4 In Table 7 and Figures 3-6, we summarized the average size of droplets and PDI for all the SEDDS. We measured polydispersity as the ratio of the standard devia- Our results are shown in Figures 12 and 13.…”

“…2,3 There are plenty of theories explaining the etiology of the syndrome but it is generally agreed that the factors involved are either myogenic, neurogenic and/or integrative (trigger-mediated). 4 OAB may have a deleterious effect on quality of life since it considerably affects the occupational, physical and sexual activities of the patients. Thus, it can lead to impaired work productivity, sleep disturbances, social isolation and depression 5 OAB with urge incontinence is also a major reason for hospital admissions among the elderly.…”

Intravesical liposome therapy for interstitial cystitis

“…There were no reports of large PVR, urinary retention or UTI in treated patients during the follow‐up period. Liposomes are a suitable intravesical delivery platform for potent toxins, as reviewed here …”