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

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.