Enhancing intravesical bladder cancer therapy: from mucoadhesive to targeted drug delivery strategies.

Intravesical administration is a standard application route for the treatment of non-muscle-invasive bladder cancer, as it allows for high drug concentrations near tumor sites while largely avoiding systemic exposure and associated adverse effects. However, the efficacy can be constrained by the urothelium's strong barrier properties, as well as continuous dilution and elimination of drugs through urine production and voiding. Bladder-retentive drug delivery systems, such as intravesical sustained-release formulations that accumulate therapeutics at the bladder wall or active targeting to tumor cells may address these limitations. In this context, mucoadhesive formulations are promising because they resist urinary washout, extend dwell time, and enhance urothelial drug deposition. Targeted delivery platforms can increase drug load within malignant tissues and may even accelerate onset of pharmacologic activity via receptor mediated pathways. If binding to tumor-specific target structures also modulates the disease itself, active targeting can extend beyond pharmacokinetic benefits to integrate different pharmacodynamic mechanisms, thereby contributing to more precise and effective cancer therapy. Several targeted intravesical drug formulations, including antibody-drug conjugates against tumor associated antigens, integrin directed systems, hyaluronic acid-based CD44 targeted constructs, as well as immunomodulatory agents, have advanced to clinical or late preclinical evaluation. The intravesical route further provides an opportunity to repurpose drugs originally developed for systemic use but limited by off target toxicities that are unlikely to be dose limiting with local intravesical administration. This mini review provides an overview of intravesical, bladder-retentive systems for treating urothelial carcinoma, with a particular emphasis on recent developments in tumor-targeted intravesical precision medicines.