Delivery of Intravesical Botulinum Toxin A Using Low Energy Shock Waves in Treatment of Overactive Bladder: A Feasibility Study

High energy extracorporeal shock wave thrapy has been used to disintegrate urolithiasis for 30 years (Chaussy et al., 1982). Low energy shock wave LESWs are used clinically to improve tissue regeneration at tendon- bone junctions (Wang et al., 2003) , ischemic cardiovascular disorders (Dimeglio et al., 2012) and erectile dysfunctions (Vardi et al., 2012).

Furthermore, shock waves have been shown to temporarily increase tissue permeability (Lauer et al., 1997, Kodama et al., 2002) and increase mediated molecular and drug delivery into cells without consequent cytotoxicity. Kodama et al., 2002 suggested that shock waves could cause shear force generated by the movement of liquid relative to cells to temporarily affect the permeability of the plasma memberance. Shock waves can deliver molecules to 2,000,000 molecular weight into the cystoplasm of cells without toxicity (Lauer et al., 1997).

Instillation of drugs in the bladder provides the opportunity to locally increase drug concentration with a low risk of systemic side effects (Kuo et al., 2010, Hsu et al., 2013). Intravesical pharmacotherapy has been used to treat refractory overactive bladder and interstitial cystitis/ painful bladder syndrome (smith et al., 2004; Grannantoni et al., 2008; Boy et al., 2006). However, drug delivery to bladder tissues by intravesical route is constrained by urothelial impermeability. The watertight barrier is generally located at the umbrella cells, which are the superficial layers of bladder epithelium augmented by glycosaminoglycans and uroplakins (Hsu et al., 2013; Birder et al., 2005).

Transient permeabilization of cell membranes accomplished by shock waves can deliver macromolecular drugs in the bladder without toxicity (Lower et al., 1997; Kodama et al., 2002).

Chuang et al., (2016) demonstrated that contrast enhanced MRI can detect increased rat bladder permeability after LESWs. Recently, Towner et al (2015) reported increased urothelial permeability and contrast leakage on bladder MRI after intravesical promtamine sulfate instillation.