Visualized Intravesical Floating Hydrogel Encapsulating Vaporized Perfluoropentane For Controlled Drug Release

Disorders in urinary bladder include bladder cancer (BCa), interstitial cystitis or painful bladder syndrome (IC/PBS) and overactive bladder (OAB). Among these, bladder cancer and interstitial cystitis are major diseases. In 2014,74690 bladder cancer cases and 15580 deaths were estimated in the United States, occupying 4.5% and 2.6% of all cancer cases, respectively. Systemic administration of drugs is ineffective for the treatment of bladder diseases, since it fails to achieve a sufficient effect at the diseased site. Local delivery of drugs include injections directly into the bladder muscle, intravesical instillations and indwelling physical devices. Intravesical instillations involve instilling chemical drugs to bladder using a urethral catheter. Unlike systemic administration, drugs will directly reach the diseased site with few systemic side effects.In this study, we developed a visualized floating hydrogel for intravesical drug delivery. The visualized intravesical floating hydrogel uses perfluoropentane (PFP) as the floating agent and the visualizing agent. After intravesical instillation of the visualized floating hydrogel, the increased temperature in bladder vaporized PFP, resulting in generation of microbubbles in hydrogel. Hence the hydrogel can float in urine to avoid the urinary obstruction and bladder irritation. Furthermore, perfluoropentane is biologically inert and widely used as contrast agents for diagnosis. Our study showed that the B ultrasound images of this floating hydrogel were much clearer than previous floating hydrogels. Therefore, our hydrogel can be monitored clearly via B ultrasound during the injection and floating process of hydrogel in the bladder. In vivo efficacy experiments demonstrated that the drug efficiency is much better than free drugs and non-floating hydrogels.The visualized floating hydrogel can effectively reduce the relief arising from frequent intravesical instillation for drug solution, reduce the risk of urinary obstruction and bladder irritation by intravesical instillation of mucoadesive hydrogel, and increase the contrast of B ultrasound images. Therefore, this new drug delivery system addresses the problems of conventional intravesical instillation and is promising for clinic use.