2. Academic Validation
  3. Spiky Nanoparticle-Gel Composite for Efficient Intravesical Botulinum Toxin A Delivery and Treatment of Overactive Bladder

Spiky Nanoparticle-Gel Composite for Efficient Intravesical Botulinum Toxin A Delivery and Treatment of Overactive Bladder

  • Adv Healthc Mater. 2026 Jun;15(21):e05843. doi: 10.1002/adhm.202505843.
Yongheng Zhou 1 2 3 4 5,  Qinggang Liu 6,  Linna Wang 7,  Haoyu Sun 8,  Yixi Liu 2 4 9,  Tianyu Xiang 2 4 9,  Meikai Zhu 1 2 3 4 5,  Xin Liu 2 4 9,  Tao Liu 2 4 9,  Huiling Cong 2 4 9,  Limin Liao 1 2 3 4 5 9
Affiliations

Affiliations

  • 1 Department of Urology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
  • 2 Department of Urology, China Rehabilitation Research Center, Beijing, China.
  • 3 University of Health and Rehabilitation Sciences, Qingdao, Shandong, China.
  • 4 China Rehabilitation Science Institute, Beijing, China.
  • 5 Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China.
  • 6 Department of Urology, Qingdao Municipal Hospital, Qingdao, China.
  • 7 Lanzhou Biotechnique Development Co., Ltd, Lanzhou, Gansu, China.
  • 8 Department of Urology, The Second Qilu Hospital of Shandong University, Jinan, Shandong, China.
  • 9 School of Rehabilitation, Capital Medical University, Beijing, China.
PMID: 41889245 DOI: 10.1002/adhm.202505843
Abstract

Overactive bladder (OAB) is a symptomatic disease that is difficult to treat. This study developed APTES-functionalized spiky titanium dioxide nanoparticles (ASNPs) loaded with botulinum toxin A (ASNP@BA), which is coated with P407/HA (HP) thermosensitive gel to treat OAB. Spiky nanoparticles exhibited a spiky nanostructure and were APTES-functionalized to exhibit enhanced drug-loading capacity. The optimal HP gel changed from liquid to gel near body temperature. In vitro, ASNPs enter cells via MYH9-mediated endocytosis. The expression of ZO-1 and E-cadherin proteins, along with changes in TEER, indicates that ASNPs entering cells do not compromise the integrity of the bladder barrier. In vivo, ASNP@HP showed excellent biocompatibility. Following bladder instillation of ASNP@HP, no significant toxicity was observed in major organs. The bladder barrier integrity was not significantly compromised. In a rat model, pretreatment of the bladder with ASNP@HPBA significantly reduced the excessive contraction induced by acetic acid, markedly reducing the intercontraction interval decline to 41.83% ± 17.78% compared to controls (∼75%) and free BTX-A (71.72%). The downregulation of SNAP-25 and SNAP-23 in the ASNP@HPBA group demonstrated successful targeted delivery and bioactivity. This platform combines macromolecular drug delivery with effective therapeutic efficacy and safety profile, representing a promising strategy for the treatment of OAB.

Keywords

botulinum toxin A; drug delivery; overactive bladder; spiky nanoparticle.

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