Interstitial Cystitis / Bladder Pain Syndrome (IC/BPS) is defined as persistent or recurrent chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom such as an urgent need to void or urinary frequency. Diagnosed in the absence of any identifiable pathology which could explain these symptoms. According to AUA guidelines, intravesical treatments with DMSO, heparin, or lidocaine may be administered as second-line treatments, hydrodistension under anesthesia considered as third-line treatment. And in difficult cases of IC/BPS, intravesical (intradetrusor) botulinum toxin A (BTX-A) may be administered as a fourth-line treatment option [1]. Compared to bladder instillation, intravesical injection requires general anesthesia and cystoscopic guided needle injection. Intravesical injection of botox is a more invasive procedure compared to intravesical installation which can be performed under local anesthesia. Thus we invented “encapsulated-botulinum toxin A mucoadhesive nanoparticles (EBMN)”. The nanoparticles can be formed under simply physiological ultrasonic oscillation.

We used HCl bladder instillation on female rat model for mimicking interstitial cystitis / bladder pain syndrome (IC/BPS). We divided the rats into 3 groups, the first as control group which received bladder instillation with normal saline, the second group as HCl group which received bladder instillation with HCl for 1.5 hours, and the final group as HCl + EBMN group which received 2ml EBMN bladder instillation with 1.2ml/hour in the next day following HCl bladder instillation. The EBMN was prepared with Botulinum toxin (Botox, Allergan), Hyaluronic acid (cystistat, Mylan), Alginate (Sigma-Aldrich), and Gelatin (Fluka Analytical). We did the transcystogram for recording amplitude, duration of voiding contraction, and intercontraction interval. We also did Western blot for measuring the level of synaptosome-associated protein of 25 kDa (SNAP-25), an immunoreactive fiber abundant throughout the bladder tissue in the mucosa and muscular layer, of the whole bladder following rats were sacrificed.

We found HCl-induced cystitis on rats treated with the encapsulated-botulinum toxin A mucoadhesive nanoparticles (EBMN) showed improved voiding frequency on transcystogram. Western blot revealed that HCl-induced cystitis treated with the EBMN, level of SNAP-25 decreased.

The results showed encapsulated-botulinum toxin A mucoadhesive nanoparticles (EBMN) releases botox into bladder submucosa only via bladder instillation. The results suggested promising therapeutic effects of EBMN with conservative bladder instillation.

Instillation with the new drug, encapsulated-botulinum toxin A mucoadhesive nanoparticles (EBMN), effectively ameliorated bladder hyperactivity induced by HCl instillation. The results implied urothelial injured diseases might be also beneficial from EBMN instillation.

Hanno PM, Erickson D, Moldwin R et al: Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol 2015; 193: 1545.