Advertisement

Neurourology pp 299-302 | Cite as

Botulinum Toxin and the Bladder: Future Research Directions

  • Apostolos Apostolidis
Chapter

Abstract

As the method for intradetrusor injections of BoNT/A has not been standardised yet for maximization of efficacy and safety and while the injection technique remains minimally invasive with some assorted patient discomfort and potential transient complications from the injections [1], several injection-free techniques have or are being tested in preclinical and clinical studies [2]. Plain intravesical instillation of BoNT/A, intravesical delivery of BoNT/A via electromotive-drug administration or following bladder treatment with protamine sulphate or low-energy shock-waves, instillation of BoNT/A mixed with dimethyl sulfoxide (DMSO), conjugated with liposomes or cationic peptides and complexed with thermosensitive hydrogel are some of the novel techniques under investigation [2]. Almost all techniques aim at increasing the toxin’s permeability via the urothelium.

References

  1. 1.
    Mangera A, Andersson KE, Apostolidis A, et al. Contemporary management of lower urinary tract disease with botulinum toxin A: a systematic review of botox (onabotulinumtoxinA) and dysport (abobotulinumtoxinA). Eur Urol. 2011;60:784–95.CrossRefGoogle Scholar
  2. 2.
    Tyagi P, Kashyap M, Yoshimura N, et al. Past, present and future of chemodenervation with botulinum toxin in the treatment of overactive bladder. J Urol. 2017;197:982–90.CrossRefGoogle Scholar
  3. 3.
    Krhut J, Zvara P. Intravesical instillation of botulinum toxin A: an in vivo murine study and pilot clinical trial. Int Urol Nephrol. 2011;43:337–43.CrossRefGoogle Scholar
  4. 4.
    Chuang YC, Yoshimura N, Huang CC, et al. Intravesical botulinum toxin A administration inhibits COX-2 and EP4 expression and suppresses bladder hyperactivity in cyclophosphamide-induced cystitis in rats. Eur Urol. 2009;56:159–66.CrossRefGoogle Scholar
  5. 5.
    Kajbafzadeh AM, Ahmadi H, Montaser-Kouhsari L, et al. Intravesical electromotive botulinum toxin type A administration-part II: clinical application. Urology. 2011;77:439–45.CrossRefGoogle Scholar
  6. 6.
    Ladi-Seyedian SS, Sharifi-Rad L, Kajbafzadeh AM. Intravesical electromotive botulinum toxin type “A” administration for management of urinary incontinence secondary to neuropathic detrusor overactivity in children: long-term follow-up. Urology. 2018;114:167–74.CrossRefGoogle Scholar
  7. 7.
    Chen D, Song D, Wientjes MG, et al. Effect of dimethyl sulfoxide on bladder tissue penetration of intravesical paclitaxel. Clin Cancer Res. 2003;9:363–9.PubMedGoogle Scholar
  8. 8.
    Shimizu S, Wheeler M, Saito M. Effect of intravesical botulinum toxin A delivery (using DMSO) in rat overactive bladder model. J Urol Suppl. 2012;187:907.CrossRefGoogle Scholar
  9. 9.
    Petrou SP, Parker AS, Crook JE, et al. Botulinum a toxin/dimethyl sulfoxide bladder instillations for women with refractory idiopathic detrusor overactivity: a phase 1/2 study. Mayo Clin Proc. 2009;84:702–6.CrossRefGoogle Scholar
  10. 10.
    Khera M, Somogyi GT, Salas NA, et al. In vivo effects of botulinum toxin A on visceral sensory function in chronic spinal cord-injured rats. Urology. 2005;66:208–12.CrossRefGoogle Scholar
  11. 11.
    Glogau R, Blitzer A, Brandt F, et al. Results of a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a botulinum toxin type A topical gel for the treatment of moderate-to-severe lateral canthal lines. J Drugs Dermatol. 2012;11:38–45.PubMedGoogle Scholar
  12. 12.
    Rajaganapathy BR, Chancellor MB, Nirmal J, et al. Bladder uptake of liposomes after intravesical administration occurs by endocytosis. PLoS One. 2015;10:e0122766.CrossRefGoogle Scholar
  13. 13.
    Shone CC, Hambleton P, Melling J. A 50-kDa fragment from the NH2-terminus of the heavy subunit of clostridium botulinum type A neurotoxin forms channels in lipid vesicles. Eur J Biochem. 1987;167:175–80.CrossRefGoogle Scholar
  14. 14.
    Montecucco C, Schiavo G, Gao Z, et al. Interaction of botulinum and tetanus toxins with the lipid bilayer surface. Biochem J. 1988;251:379–83.CrossRefGoogle Scholar
  15. 15.
    de Paiva A, Dolly JO. Light chain of botulinum neurotoxin is active in mammalian motor nerve terminals when delivered via liposomes. FEBS Lett. 1990;277:171–4.CrossRefGoogle Scholar
  16. 16.
    Nirmal J, Wolf-Johnston AS, Chancellor MB, et al. Liposomal inhibition of acrolein-induced injury in rat cultured urothelial cells. Int Urol Nephrol. 2014;46:1947–52.CrossRefGoogle Scholar
  17. 17.
    Janicki JJ, Chancellor MB, Kaufman J, et al. Potential effect of liposomes and liposome-encapsulated botulinum toxin and tacrolimus in the treatment of bladder dysfunction. Toxins (Basel). 2016;8:81.CrossRefGoogle Scholar
  18. 18.
    Kuo HC, Liu HT, Chuang YC, et al. Pilot study of liposome-encapsulated onabotulinumtoxina for patients with overactive bladder: a single-center study. Eur Urol. 2014;65:1117–24.CrossRefGoogle Scholar
  19. 19.
    Chuang YC, Kaufmann JH, Chancellor DD, et al. Bladder instillation of liposome encapsulated onabotulinumtoxina improves overactive bladder symptoms: a prospective, multicenter, double-blind, randomized trial. J Urol. 2014;192:1743–9.CrossRefGoogle Scholar
  20. 20.
    Chuang YC, Tyagi P, Huang CC, et al. Urodynamic and immunohistochemical evaluation of intravesical botulinum toxin A delivery using liposomes. J Urol. 2009;182:786–92.CrossRefGoogle Scholar
  21. 21.
    Chuang YC, Lee WC, Lee WC, et al. Intravesical liposome versus oral pentosan polysulfate for interstitial cystitis/painful bladder syndrome. J Urol. 2009;182:1393–400.CrossRefGoogle Scholar
  22. 22.
    Peters KM, Hasenau D, Killinger KA, et al. Liposomal bladder instillations for IC/BPS: an open-label clinical evaluation. Int Urol Nephrol. 2014;46:2291–5.CrossRefGoogle Scholar
  23. 23.
    Chuang YC, Kuo HC. A prospective, multicenter, double-blind, randomized trial of bladder instillation of liposome formulation onabotulinumtoxinA for interstitial cystitis/bladder pain syndrome. J Urol. 2017;198(2):376–82.CrossRefGoogle Scholar
  24. 24.
    Stav K, Vinshtok Y, Jeshurun M, et al. PD20–03 pilot study evaluating safety and feasibility of intravesical instillation of botulinum toxin in hydrogel-based slow release delivery system in PBS/IC patients. J Urol Suppl. 2015;193:e398.CrossRefGoogle Scholar
  25. 25.
    Krhut J, Navratilova M, Sykora R, et al. Intravesical instillation of onabotulinum toxin A embedded in inert hydrogel in the treatment of idiopathic overactive bladder: a double-blind randomized pilot study. Scand J Urol. 2016;50:200–5.CrossRefGoogle Scholar
  26. 26.
    Chuang YC, Huang TL, Tyagi P, et al. Urodynamic and immunohistochemical evaluation of intravesical botulinum toxin A delivery using low energy shock waves. J Urol. 2016;196:599–608.CrossRefGoogle Scholar
  27. 27.
    Jin Y, Xu L, Zhao Y, et al. Endogenous stem cells were recruited by defocused low-energy shock wave in treating diabetic bladder dysfunction. Stem Cell Rev. 2017;13:287–98.CrossRefGoogle Scholar
  28. 28.
    Pickett A, Perrow K. Towards new uses of botulinum toxin as a novel therapeutic tool. Toxins (Basel). 2011;3:63–81.CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Apostolos Apostolidis
    • 1
  1. 1.Second Department of UrologyAristotle University of Thessaloniki, General Hospital ‘Papageorgiou’ThessalonikiGreece

Personalised recommendations