Prolonged Release of Bacillus Calmette–Guérin by Floating Microbubbles to Enhance Intravesical Immunotherapy for Bladder Cancer

Intravesical Bacillus Calmette–Guérin (BCG) immunotherapy is a standard treatment for intermediate-risk and high-risk nonmuscle-invasive bladder cancer. The prolonged duration of BCG in the bladder can enhance the immunotherapeutic efficacy. However, intravesical BCG is rapidly excreted with urine by urination at 2 h postinstillation, compromising therapeutic outcomes. Here, this study develops a floating drug delivery system based on air microbubbles to achieve long-term retention of BCG in the bladder. By encapsulating BCG within floating air microbubbles, we successfully develop BCG-loaded microbubbles (BCG-MBs) that are capable of prolonged release of BCG in the bladder. Compared with conventional intravesical BCG immunotherapy, intravesical instillation of BCG-MBs induces more durable immune responses and demonstrates enhanced therapeutic efficacy in SD rats with orthotopic bladder cancer. Furthermore, the floating drug delivery system based on air-microbubbles not only represents a potential intravesical drug carrier for bladder cancer, but also a versatile platform that can encapsulate diverse therapeutic agents, thereby showing great potential applications in immunotherapy, targeted drug delivery, and combination therapy.