Urodynamic and Immunohistochemical Evaluation of Intravesical Botulinum Toxin A Delivery Using Liposomes

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Abstract

Purpose: Botulinum toxin A (Allergan, Irvine, California) is a high molecular weight neurotoxin used to treat hypersensitive bladder by direct injection to pass the urothelial barrier. We investigated the feasibility of intravesical botulinum toxin A delivery using liposomes (Lipella Pharmaceuticals, Pittsburgh, Pennsylvania), which are phospholipid bilayered vesicles, and evaluated the urodynamic and immunohistochemical effect on acetic acid induced bladder hyperactivity in rats. Materials and Methods: Liposomes (1 ml), botulinum toxin A (20 U/1 ml saline) or botulinum toxin A encapsulated in liposomes (lipotoxin, that is 20 U botulinum toxin A plus 1 ml liposomes) was administered in the bladder and retained for 1 hour on day 1 after baseline cystometrogram. Continuous cystometrogram was performed on day 1 by filling the bladder with saline and on day 8 by filling the bladder with saline, followed by 0.3% acetic acid. The bladder was then harvested. Cystometrogram parameters, histology, SNAP25 and calcitonin gene-related peptide expression were measured by Western blotting or immunostaining. Results: The intercontraction interval was decreased 57.2% and 56.0% after intravesical acetic acid instillation in liposome and botulinum toxin A pretreated rats, respectively. However, rats that received lipotoxin showed a significantly decreased intercontraction interval response (21.1% decrease) to acetic acid instillation but without compromised voiding function. Also, lipotoxin pretreated rats had a better decrease in the inflammatory reaction and SNAP-25 expression, and increase in calcitonin gene-related peptide immunoreactivity than those in liposome or botulinum toxin A pretreated rats. Conclusions: Intravesical lipotoxin administration cleaved SNAP-25, inhibited calcitonin gene-related peptide release from afferent nerve terminals and blocked the acetic acid induced hyperactive bladder. These results support liposomes as an efficient vehicle for delivering botulinum toxin A without injection. © 2009 American Urological Association.

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Chuang, Y. C., Tyagi, P., Huang, C. C., Yoshimura, N., Wu, M., Kaufman, J., & Chancellor, M. B. (2009). Urodynamic and Immunohistochemical Evaluation of Intravesical Botulinum Toxin A Delivery Using Liposomes. Journal of Urology, 182(2), 786–792. https://doi.org/10.1016/j.juro.2009.03.083

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