title: Pilot study of liposome-encapsulated onabotulinumtoxina for patients with overactive bladder: a single-center study.
abstract: BACKGROUND
  Intradetrusor onabotulinumtoxinA (BoNT-A) injection benefits overactive bladder (OAB) patients, but increased postvoid residual (PVR) urine volume and urinary tract infection (UTI) remain risks. Intravesical instillation of liposomal BoNT-A instead of injection could prevent such adverse events.
  
  
  OBJECTIVE
  To evaluate instillation of liquid liposomal BoNT-A (Lipotoxin) for the treatment of OAB and to determine its mechanism of action.
  
  
  METHODS
  A double-blind randomized parallel controlled pilot trial in 24 OAB patients at a single tertiary center.
  
  
  METHODS
  Patients were randomly assigned to intravesical instillation of Lipotoxin containing 80 mg liposomes and 200 U BoNT-A or normal saline (N/S). Patients were retreated with Lipotoxin 1 mo later if they failed the first treatment.
  
  
  METHODS
  Voiding diaries, OAB symptom scores, urodynamic studies, and adverse events were monitored. The primary end point was change of total urinary frequency per 3 d at 1 mo after treatment. Immunohistochemistry and Western blotting for synaptic vesicle glycoprotein 2A (SV2A) and synaptosomal-associated protein, 25 kDa (SNAP25) were performed at baseline and 3 mo after treatment. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis.
  
  
  CONCLUSIONS
  At 1 mo after treatment, the change of urinary frequency per 3 d significantly improved in the Lipotoxin group (n=12; median: -6.50; interquartile range [IQR]: -18.3 to -0.25; p=0.008) but not in the N/S group. (n=12.0; IQR: -7.75 to 8.0; p=0.792). Urgency episodes also showed a significant decrease in the Lipotoxin group (-12.0; IQR: -20.3 to -2.75; p=0.012) but not in the N/S group (-1.0; IQR: -11.0 to 2.5; p=0.196). SV2A and SNAP25 were expressed in urothelial cells and suburothelial tissues. However, the protein expression did not significantly differ between responders and nonresponders at 3 mo after treatment.
  
  
  CONCLUSIONS
  Intravesical Lipotoxin instillation effectively reduced frequency episodes 1 mo after treatment in OAB patients without any increase in PVR or risk of UTI.
  
  
  RESULTS
  We demonstrated that intravesical Lipotoxin instillation reduced frequency episodes at 1 mo in overactive bladder patients. This procedure is safe, without an increase in postvoid residual or the risk of urinary tract infection.
authors.affiliation: Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan. Electronic address: hck@tzuchi.com.tw.
authors.forename: Hann-Chorng
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan; Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
authors.forename: Hsin-Tzu
authors.initials: HT
authors.lastname: Liu
authors.affiliation: Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yao-Chi
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: Departments of Medicine and Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Birder
authors.affiliation: Oakland University, William Beaumont School of Medicine, Royal Oak, MI, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
mesh_terms: D065087:Acetylcholine Release Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008081:Liposomes; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis; D010865:Pilot Projects; D050825:Synaptosomal-Associated Protein 25 / Q000032:analysis; D001743:Urinary Bladder / Q000737:chemistry; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D019459:Urothelium / Q000737:chemistry
chemical_list: D065087:Acetylcholine Release Inhibitors; D008081:Liposomes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050825:Synaptosomal-Associated Protein 25; C076414:SV2A protein, human; D019274:Botulinum Toxins, Type A
keywords: Botulinum toxin; Liposome; Overactive bladder; Urothelium