The new therapeutic options are aimed at reducing the maximum symptoms, as well as the induced side effects. Intravesical delivery of anticholinergics is becoming a promising alternative for patients who fail oral therapies. Intravesical Antimuscarinic A recent study showed that intravesically administered anticholinergic drugs, apart from blocking muscarinic
receptors in the bladder, may also be acting through blockade of bladdercooling reflex mediated by C-fibers in most patients with incomplete neurogenic lesion and detrusor overactivity. 19 Modified Inhibitors,research,lifescience,medical intravesical oxybutynin (1.25 mg/5 mL, twice daily) was shown to be an effective and relatively safe therapeutic option for children with neurogenic bladders who were either unresponsive to, or experienced intolerable side Lonafarnib research buy effects from, oral medications.20 Improvements in both cystometric bladder capacity and compliance were noted in all patients after 1 week, and detrusor overactivity was undetectable in 3 of 4 patients. At 1 year, there was further improvement Inhibitors,research,lifescience,medical in bladder compliance in 3 patients, and detrusor overactivity was not observed in 2 patients. The severity of incontinence was significantly improved, and none of the side effects of oral anticholinergics were observed in any of the patients. A single Inhibitors,research,lifescience,medical patient with vesicoureteral reflux discontinued the therapy after 2 months due to
upper urinary tract infections (UTIs). Botulinum Neurotoxin In the field of neurourology, instillation Inhibitors,research,lifescience,medical of neurotoxins into the bladder is an accepted approach to achieve chemical neuromodulation of afferent neurotransmission underlying neurogenic bladder or OAB.21 Cystoscope-guided injections continue to remain the gold standard for administering botulinum neurotoxin (BoNT) to the bladder. Intravesical instillation of BoNT alone in animal models of bladder irritation has been evaluated Inhibitors,research,lifescience,medical in the past with mixed results.22 Several reasons have been surmised for the lack of efficacy from BoNT instillation such as protein degradation by proteases and proteinases in urine, dilution in
urine, or poor uptake of the BoNT solution into the urothelium. Neuromodulation of bladder afferents by different intravesical neurotoxins is therefore limited by either solvent toxicity23 or degradation from proteases in urine. Liposomes have been previously studied as else a carrier of toxins to enhance their efficacy at lower doses.24 The lipid vesicles comprise either one or several aqueous compartments delineated by either one (unilamellar) or several (multilamellar) phospholipid bilayers.12 In the context of toxins instilled in the bladder, fat-soluble neurotoxins such as capsaicin can be integrated into the phospholipid bilayer25 and water-soluble neurotoxins such as botulinum can be protected inside the aqueous compartment(s) of liposomes delimited by the phospholipid bilayer(s)26 (Figure 2).