Abstract

Recurrent urinary tract infection (rUTI) continues to pose a formidable clinical challenge, largely owing to the rapid clearance of therapeutic agents from the bladder caused by short intravesical residence time and periodic urinary voiding. Although intravesical drug delivery has emerged as a promising local therapeutic strategy, conventional liquid instillations and physically crosslinked hydrogels frequently fail to sustain structural integrity and prolonged drug release within the dynamically changing bladder microenvironment. Herein, we develop a photocrosslinkable, pH-responsive intravesical floating drug delivery system (iFDDS) for sustained antimicrobial delivery. This system is fabricated using diacrylated Pluronic F127 (F127DA) as the core network-building component. The covalently crosslinked F127DA network confers superior mechanical stability while preserving amphiphilic micellar domains that enable efficient loading of hydrophobic drugs. A tertiary amine-based pH-responsive crosslinker (CLMA) is further integrated into the hydrogel matrix, endowing iFDDS with enhanced swelling capacity under the mildly acidic microenvironment. Additionally, lyophilization-induced porous architecture reduces the apparent density of the iFDDS below that of urine, achieving stable flotation for over 48 h and effectively mitigating the risk of urinary tract obstruction. The optimized iFDDS exhibits favorable catheter deliverability, shear-thinning rheological behavior adaptable to dynamic fluid conditions, and excellent biocompatibility with bladder epithelial cells. Upon loading with rifampicin, the iFDDS demonstrates potent and sustained antibacterial efficacy against Escherichia coli. This study establishes a robust, environment-adaptive platform for intravesical therapy, offering a viable strategy to address the short residence time limitation of conventional formulations and improve the therapeutic management of rUTI.

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