{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:42:07Z","timestamp":1793234527914,"version":"4.5.0"},"reference-count":64,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum toxin type A (BoNT\/A) injection into the bladder wall is a milestone in the treatment of urinary incontinence in patients with neurogenic detrusor overactivity (NDOi) or overactive bladder syndrome (OABi) who are refractory to or unable to tolerate oral or transdermal therapies. However, the efficacy of BoNT\/A is hampered by the low long-term adherence of patients to a treatment that requires repeated bladder injections under cystoscopy control. The discontinuation is particularly evident among incontinent patients with spontaneous voluntary voiding, regardless of whether the cause is NDOi or OABi, although clearly more marked among the latter group. In addition to the bother and pain associated with repeated cystoscopies, these patients show low tolerance to the high incidence of urinary tract infections (UTIs) and transient urinary retention, the two most common adverse events. Fewer injection points may render treatments less painful, apparently without reducing efficacy, but will not avoid the need for repeated cystoscopies, and no studies have demonstrated that such modification increases adherence. Eventually, accessing the bladder wall for BoNT\/A administration via a transabdominal approach, under real-time ultrasound guidance, may overcome trans-urethral limitations, but the technique\u2019s reproducibility remains unknown. An intensive investigation is ongoing to identify aids that facilitate the passage of the large, fragile BoNT\/A molecule across the urothelium to reach the bladder nerves without injections. Electromotive Drug Administration (EMDA) of BoNT\/A demonstrated efficacy and safety over a 6-year follow-up in NDOi patients at a single center, but the results were not reproduced at other institutions. The application of shock waves to the bladder using shock waves generated by Extracorporeal Shock Wave Lithotripsy (ESWL) machines to tear the urothelium and facilitate the passage of BoNT\/A instilled in the bladder is ingenious, but the experience is very limited. Dimethyl sulfoxide, liposomes, and thermal-reversal hydrogel to deliver the toxin failed in pilot trials. BoNT\/A in nano-formulations has high heat stability, resistance to pH changes, and to enzymatic degradation. Extended efficacy in dermal and intramuscular pilot applications is promising but needs to be replicated in the bladder.<\/jats:p>","DOI":"10.3390\/toxins18040170","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T10:09:21Z","timestamp":1775038161000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Botulinum Toxin Type A Injections in the Bladder Wall\u2014An Effective Treatment for Urinary Incontinence with Low Long-Term Adherence"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4551-514X","authenticated-orcid":false,"given":"Francisco","family":"Cruz","sequence":"first","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Urology, Hospital S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"RISE-Health Institute for Research, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4161-8467","authenticated-orcid":false,"given":"Martin C.","family":"Michel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany"},{"name":"Pharmaceutical Medicine, Charlotte Fresenius University, 65185 Wiesbaden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Igawa","sequence":"additional","affiliation":[{"name":"Department of Urology, Nagano Prefectural Shinshu Medical Center, 1332 Suzaka, Nagano 382-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","unstructured":"(2025, December 18). EAU Guidelines on Non-Neurogenic Female LUTS\u2014Introduction. Available online: https:\/\/uroweb.org\/guidelines\/non-neurogenic-female-luts\/chapter\/introduction."},{"key":"ref_2","unstructured":"American Urological Association (2025, December 18). Incontinence Guidelines. Available online: https:\/\/www.auanet.org\/guidelines-and-quality\/guidelines\/non-oncology-guidelines\/incontinence."},{"key":"ref_3","unstructured":"ICS (2025, December 18). Incontinence 7th Edition. Available online: https:\/\/www.ics.org\/ici."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/nau.22445","article-title":"Targets for Botulinum Toxin in the Lower Urinary Tract","volume":"33","author":"Cruz","year":"2014","journal-title":"Neurourol. Urodyn."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1124\/pharmrev.121.000523","article-title":"Current and Emerging Pharmacological Targets and Treatments of Urinary Incontinence and Related Disorders","volume":"75","author":"Michel","year":"2023","journal-title":"Pharmacol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"eAO4207","DOI":"10.1590\/s1679-45082018ao4207","article-title":"Intradetrusor OnabotulinumtoxinA Injections Are Significantly More Efficacious than Oral Oxybutynin for Treatment of Neurogenic Detrusor Overactivity: Results of a Randomized, Controlled, 24-Week Trial","volume":"16","author":"Ferreira","year":"2018","journal-title":"Einstein"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/bju.13945","article-title":"Comparative Assessment of the Efficacy of OnabotulinumtoxinA and Oral Therapies (Anticholinergics and Mirabegron) for Overactive Bladder: A Systematic Review and Network Meta-Analysis","volume":"120","author":"Drake","year":"2017","journal-title":"BJU Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.eururo.2011.07.002","article-title":"Efficacy and Safety of OnabotulinumtoxinA in Patients with Urinary Incontinence Due to Neurogenic Detrusor Overactivity: A Randomised, Double-Blind, Placebo-Controlled Trial","volume":"60","author":"Cruz","year":"2011","journal-title":"Eur. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1016\/j.juro.2012.01.125","article-title":"Phase 3 Efficacy and Tolerability Study of OnabotulinumtoxinA for Urinary Incontinence from Neurogenic Detrusor Overactivity","volume":"187","author":"Ginsberg","year":"2012","journal-title":"J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.eururo.2022.03.010","article-title":"Efficacy and Safety of AbobotulinumtoxinA in Patients with Neurogenic Detrusor Overactivity Incontinence Performing Regular Clean Intermittent Catheterization: Pooled Results from Two Phase 3 Randomized Studies (CONTENT1 and CONTENT2)","volume":"82","author":"Kennelly","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e657","DOI":"10.1212\/WNL.0000000000005991","article-title":"Low-Dose OnabotulinumtoxinA Improves Urinary Symptoms in Noncatheterizing Patients with MS","volume":"91","author":"Tullman","year":"2018","journal-title":"Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1111\/bju.13795","article-title":"Positive Outcomes with First OnabotulinumtoxinA Treatment Persist in the Long Term with Repeat Treatments in Patients with Neurogenic Detrusor Overactivity","volume":"119","author":"Denys","year":"2017","journal-title":"BJU Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.eururo.2013.04.001","article-title":"OnabotulinumtoxinA 100 U Significantly Improves All Idiopathic Overactive Bladder Symptoms and Quality of Life in Patients with Overactive Bladder and Urinary Incontinence: A Randomised, Double-Blind, Placebo-Controlled Trial","volume":"64","author":"Chapple","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1016\/j.juro.2012.12.022","article-title":"OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial","volume":"189","author":"Nitti","year":"2013","journal-title":"J. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/nau.22934","article-title":"Efficacy and Safety of OnabotulinumtoxinA Therapy Are Sustained over 4 Years of Treatment in Patients with Neurogenic Detrusor Overactivity: Final Results of a Long-Term Extension Study","volume":"36","author":"Kennelly","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.eururo.2007.09.034","article-title":"Neurogenic Detrusor Overactivity Treated with English Botulinum Toxin A: 8-Year Experience of One Single Centre","volume":"53","author":"Filocamo","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.juro.2016.03.146","article-title":"Durable Efficacy and Safety of Long-Term OnabotulinumtoxinA Treatment in Patients with Overactive Bladder Syndrome: Final Results of a 3.5-Year Study","volume":"196","author":"Nitti","year":"2016","journal-title":"J. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/nau.25061","article-title":"Interventions to Improve Tolerability of Local Anesthetic Intradetrusor Botulinum Toxin Injections: A Systematic Review","volume":"42","author":"Macpherson","year":"2023","journal-title":"Neurourol. Urodyn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.juro.2018.10.012","article-title":"Long-Term Discontinuation of Botulinum Toxin A Intradetrusor Injections for Neurogenic Detrusor Overactivity: A Multicenter Study","volume":"201","author":"Baron","year":"2019","journal-title":"J. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ruffion, A., Karam, P., Forestier, A., and Denys, P. (2024). Real-World Use of Intradetrusor Botulinum Toxin Injections: A Population-Based Study from France. Toxins, 16.","DOI":"10.3390\/toxins16100423"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1177\/13524585231174580","article-title":"Intravesical Injections of Botulinum Neurotoxin A to Treat Overactive Bladder and\/or Detrusor Overactivity Related to Multiple Sclerosis: 5-Year Continuation Rate and Specific Risk Factors for Discontinuation\u2014A Study from the Neuro-Urology Committee of the French Association of Urology","volume":"29","author":"Delaval","year":"2023","journal-title":"Mult. Scler."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33197","DOI":"10.1038\/srep33197","article-title":"Antibiotic Prophylaxis May Not Be Necessary in Patients with Asymptomatic Bacteriuria Undergoing Intradetrusor OnabotulinumtoxinA Injections for Neurogenic Detrusor Overactivity","volume":"6","author":"Leitner","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.juro.2017.05.068","article-title":"Long-Term Treatment with OnabotulinumtoxinA Results in Consistent, Durable Improvements in Health Related Quality of Life in Patients with Overactive Bladder","volume":"198","author":"Ginsberg","year":"2017","journal-title":"J. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1464-410X.2012.11282.x","article-title":"Long-Term Outcome of the Use of Intravesical Botulinum Toxin for the Treatment of Overactive Bladder (OAB)","volume":"111","author":"Mohee","year":"2013","journal-title":"BJU Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00345-016-1862-y","article-title":"Long-Term Follow-up of Intravesical Botulinum Toxin-A Injections in Women with Idiopathic Overactive Bladder Symptoms","volume":"35","author":"Marcelissen","year":"2017","journal-title":"World J. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.purol.2020.07.242","article-title":"Long-Term Follow-up Reveals a Low Persistence Rate of AbobotulinumtoxinA Injections for Idiopathic Overactive Bladder","volume":"30","author":"Baron","year":"2020","journal-title":"Prog. Urol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Manso, M., Soares, J.D., Henriques, M., Botelho, F., Silva, C., and Cruz, F. (2024). Efficacy, Satisfaction, and Compliance: Insights from 15 Years of Botulinum Toxin Use for Female Urgency Urinary Incontinence. Toxins, 16.","DOI":"10.3390\/toxins16080332"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1002\/nau.23196","article-title":"Long-Term Compliance and Results of Intravesical Botulinum Toxin A Injections in Male Patients","volume":"36","author":"Marcelissen","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/bju.13025","article-title":"Patient Experience and Satisfaction with Onabotulinumtoxin A for Refractory Overactive Bladder","volume":"116","author":"Malde","year":"2015","journal-title":"BJU Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/iju.12205","article-title":"Discontinuation Rates and Inter-Injection Interval for Repeated Intravesical Botulinum Toxin Type A Injections for Detrusor Overactivity","volume":"21","author":"Veeratterapillay","year":"2014","journal-title":"Int. J. Urol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1002\/nau.23224","article-title":"Beta-3 Adrenergic Receptor Is Expressed in Acetylcholine-Containing Nerve Fibers of the Human Urinary Bladder: An Immunohistochemical Study","volume":"36","author":"Coelho","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.eururo.2011.10.043","article-title":"Prospective Randomised Controlled Trial Comparing Trigone-Sparing versus Trigone-Including Intradetrusor Injection of AbobotulinumtoxinA for Refractory Idiopathic Detrusor Overactivity","volume":"61","author":"Manecksha","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.juro.2007.05.136","article-title":"Comparison of Effectiveness of Detrusor, Suburothelial and Bladder Base Injections of Botulinum Toxin a for Idiopathic Detrusor Overactivity","volume":"178","author":"Kuo","year":"2007","journal-title":"J. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.juro.2017.10.018","article-title":"Intratrigonal OnabotulinumtoxinA Improves Bladder Symptoms and Quality of Life in Patients with Bladder Pain Syndrome\/Interstitial Cystitis: A Pilot, Single Center, Randomized, Double-Blind, Placebo Controlled Trial","volume":"199","author":"Pinto","year":"2018","journal-title":"J. Urol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.eururo.2010.02.031","article-title":"Trigonal Injection of Botulinum Toxin A in Patients with Refractory Bladder Pain Syndrome\/Interstitial Cystitis","volume":"58","author":"Pinto","year":"2010","journal-title":"Eur. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/nau.20515","article-title":"Trigonal Injection of Botulinum Toxin-A Does Not Cause Vesicoureteral Reflux in Neurogenic Patients","volume":"27","author":"Mascarenhas","year":"2008","journal-title":"Neurourol. Urodyn."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.juro.2006.10.047","article-title":"Botulinum Toxin Type a Injections into the Trigone to Treat Idiopathic Overactive Bladder Do Not Induce Vesicoureteral Reflux","volume":"177","author":"Karsenty","year":"2007","journal-title":"J. Urol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.eururo.2010.06.035","article-title":"Efficacy and Tolerability of Botulinum Toxin Type a in Patients with Neurogenic Detrusor Overactivity and without Concomitant Anticholinergic Therapy: Comparison of Two Doses","volume":"58","author":"Grise","year":"2010","journal-title":"Eur. Urol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.urology.2003.12.007","article-title":"Urodynamic Evidence of Effectiveness of Botulinum a Toxin Injection in Treatment of Detrusor Overactivity Refractory to Anticholinergic Agents","volume":"63","author":"Kuo","year":"2004","journal-title":"Urology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.urology.2004.01.041","article-title":"Use of Botulinum-A Toxin for the Treatment of Refractory Overactive Bladder Symptoms: An Initial Experience","volume":"63","author":"Rapp","year":"2004","journal-title":"Urology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.eururo.2012.01.046","article-title":"Spread of OnabotulinumtoxinA after Bladder Injection. Experimental Study Using the Distribution of Cleaved SNAP-25 as the Marker of the Toxin Action","volume":"61","author":"Coelho","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00345-008-0362-0","article-title":"A Morphological Evaluation of Botulinum Neurotoxin A Injections into the Detrusor Muscle Using Magnetic Resonance Imaging","volume":"27","author":"Mehnert","year":"2009","journal-title":"World J. Urol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/nau.22954","article-title":"Efficacy and Safety of Two Administration Modes of an Intra-Detrusor Injection of 750 Units Dysport\u00ae (AbobotulinumtoxinA) in Patients Suffering from Refractory Neurogenic Detrusor Overactivity (NDO): A Randomised Placebo-Controlled Phase IIa Study","volume":"36","author":"Denys","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/nau.23052","article-title":"Less Is More-A Pilot Study Evaluating One to Three Intradetrusor Sites for Injection of OnabotulinumtoxinA for Neurogenic and Idiopathic Detrusor Overactivity","volume":"36","author":"Avallone","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.urology.2019.12.001","article-title":"Onabotulinumtoxina Re-Injection for Refractory Detrusor Overactivity Using 3-4 Injection Sites: Results of a Pilot Study","volume":"137","author":"Bonillo","year":"2020","journal-title":"Urology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/10790268.2019.1603490","article-title":"Intravesical Electromotive Administration of Botulinum Toxin Type A in Improving the Bladder and Bowel Functions: Evidence for Novel Mechanism of Action","volume":"44","author":"Kajbafzadeh","year":"2021","journal-title":"J. Spinal Cord Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.urology.2010.06.003","article-title":"Intravesical Electromotive Botulinum Toxin Type A Administration-Part II: Clinical Application","volume":"77","author":"Kajbafzadeh","year":"2011","journal-title":"Urology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.urology.2017.11.039","article-title":"Intravesical Electromotive Botulinum Toxin Type \u201cA\u201d Administration for Management of Urinary Incontinence Secondary to Neuropathic Detrusor Overactivity in Children: Long-Term Follow-Up","volume":"114","author":"Kajbafzadeh","year":"2018","journal-title":"Urology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"552.e1","DOI":"10.1016\/j.jpurol.2019.05.028","article-title":"Efficacy of Electromotive Drug Administration in Delivering Botulinum Toxin a in Children with Neuropathic Detrusor Overactivity\u2014Outcomes of a Pilot Study","volume":"15","author":"Koh","year":"2019","journal-title":"J. Pediatr. Urol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"102013","DOI":"10.1016\/j.cont.2025.102013","article-title":"Twelve-Month Experience with Intravesical Botulinum Toxin Type A Administration Using Electromotive Drug Administration for Refractory Overactive Bladder","volume":"15","author":"Gras","year":"2025","journal-title":"Continence"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1080\/2090598X.2019.1605676","article-title":"Delivery of Intravesical Botulinum Toxin A Using Low-Energy Shockwaves in the Treatment of Overactive Bladder: A Preliminary Clinical Study","volume":"17","author":"Nageib","year":"2019","journal-title":"Arab J. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.juro.2015.12.078","article-title":"Urodynamic and Immunohistochemical Evaluation of Intravesical Botulinum Toxin A Delivery Using Low Energy Shock Waves","volume":"196","author":"Chuang","year":"2016","journal-title":"J. Urol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"702","DOI":"10.4065\/84.8.702","article-title":"Botulinum A Toxin\/Dimethyl Sulfoxide Bladder Instillations for Women with Refractory Idiopathic Detrusor Overactivity: A Phase 1\/2 Study","volume":"84","author":"Petrou","year":"2009","journal-title":"Mayo Clin. Proc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/j.juro.2009.06.024","article-title":"Intravesical Liposome versus Oral Pentosan Polysulfate for Interstitial Cystitis\/Painful Bladder Syndrome","volume":"182","author":"Chuang","year":"2009","journal-title":"J. Urol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.eururo.2014.01.036","article-title":"Pilot Study of Liposome-Encapsulated OnabotulinumtoxinA for Patients with Overactive Bladder: A Single-Center Study","volume":"65","author":"Kuo","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.urology.2017.12.028","article-title":"Safety and Feasibility of Intravesical Instillation of Botulinum Toxin-A in Hydrogel-Based Slow-Release Delivery System in Patients With Interstitial Cystitis-Bladder Pain Syndrome: A Pilot Study","volume":"114","author":"Rappaport","year":"2018","journal-title":"Urology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"200","DOI":"10.3109\/21681805.2015.1121406","article-title":"Intravesical Instillation of Onabotulinum Toxin A Embedded in Inert Hydrogel in the Treatment of Idiopathic Overactive Bladder: A Double-Blind Randomized Pilot Study","volume":"50","author":"Krhut","year":"2016","journal-title":"Scand. J. Urol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/01.GOX.0000799792.25384.56","article-title":"Extended Local Release of Neuromodulators from a Novel Nanoparticle System for Chronic Migraine and Facial Aesthetics","volume":"9","author":"Harris","year":"2021","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1208\/s12249-025-03225-1","article-title":"Current Strategies in the Development of Nanoformulations to Enhance the Stability of Botox: A Systematic Review","volume":"27","author":"Ajdary","year":"2025","journal-title":"AAPS PharmSciTech"},{"key":"ref_60","unstructured":"Moeller, K.W., and Willoughby, A.J. (2022). Botulinum Toxin and Colloidal Silver Particles. (11,304,973), U.S. Patent."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"18162","DOI":"10.1038\/s41598-025-03116-2","article-title":"Ultrasound Guided Transabdominal Botulinum Toxin Injection for Refractory Overactive Bladder Treatment","volume":"15","author":"Li","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Liao, C.H., Wang, C.C., and Jiang, Y.H. (2016). Intravesical OnabotulinumtoxinA Injection for Overactive Bladder Patients with Frailty, Medical Comorbidities or Prior Lower Urinary Tract Surgery. Toxins, 8.","DOI":"10.3390\/toxins8040091"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s12325-013-0054-z","article-title":"OnabotulinumtoxinA Is Effective in Patients with Urinary Incontinence Due to Neurogenic Detrusor Overactivity Regardless of Concomitant Anticholinergic Use or Neurologic Etiology","volume":"30","author":"Ginsberg","year":"2013","journal-title":"Adv. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1007\/s43441-024-00661-2","article-title":"Regulatory Framework for Drug-Device Combination Products in the United States, Europe, and Korea","volume":"58","author":"Kim","year":"2024","journal-title":"Ther. Innov. Regul. Sci."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/4\/170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T10:20:17Z","timestamp":1775038817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/4\/170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":64,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["toxins18040170"],"URL":"https:\/\/doi.org\/10.3390\/toxins18040170","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]}}}