Long‐Term Retention Microbubbles with Three‐Layer Structure for Floating Intravesical Instillation Delivery

Abstract

Intravesical instillation is an effective treatment for bladder cancer. However, clinical anticancer agents always suffer rapid excretion by periodic urination, leading to low therapeutic efficacy. Prolonging the retention time of drugs in the bladder is the key challenge for intravesical instillation treatment. Herein, a facile and powerful surface cross‐linking‐freeze drying strategy is proposed to generate ultra‐stable albumin bovine air microbubbles (BSA‐MBs) that can float and adhere to the bladder wall to overcome the excretion of urination and exhibit a remarkable property of long‐term retention in the bladder. More noteworthy, BSA‐MBs are endowed with a specific three‐layer structure, namely, the outer membrane, middle drug loading layer and inner air core, which makes them have a low density to easily float and possess a high drug loading capacity. Based on their unique superiorities, the therapeutic potential of doxorubicin (DOX)‐loaded BSA‐MBs (DOX‐MBs) is exemplified by intravesical instillation for bladder cancer. After injection into the bladder, DOX‐MBs can remain in the bladder for a long time and sustain the release of DOX in urine, exhibiting potent anticancer efficacy. Consequently, the prolonged retention of BSA‐MBs in the bladder renders them as an effective floating drug delivery system for intravesical instillation therapy.

Encapsulation of hydroxycamptothecin within porous and hollow poly(l-lactide-co-ε-caprolactone) microspheres as a floating delivery system for intravesical instillation

“…This was primarily due to the “Cheerios effect” produced by the floating microspheres on the liquid surface, where they spontaneously gathered together or migrated to the wall by a driving force of the capillary force. 25,26 With the subsequent excretion of AU, the microspheres tended to stick to the wall instead of sinking. During the urine refilling process, the microspheres quickly floated back on the liquid surface.…”

“…Hydrogels with high viscosity could adhere to the bladder wall to prolong the intravesical residence time, but were limited by urinary tract obstruction and inflammation caused by interaction between gels and the urothelial tissue. 25,46 Nanoparticles could efficiently traverse mucosal and epithelial barriers, enabling precise drug delivery to intracellular sites of action. However, they were removed in a short time duration due to regular urination behaviors, resulting in limited therapeutic efficacy.…”