A new drug delivery system for Mitomycin C to improve intravesical instillation

Highlights: • Mitomycin C was successfully loaded onto a new delivery system for intravesical instillation. • The new delivery system exhibited excellent sustained release and prolonged retention properties. • Both hematoxylin-eosin staining for retention and mimicry of urination were adequate and innovative experiment methods. • The anti-tumor and apoptotic effect of Mitomycin C combined with the new delivery system was significantly enhanced. The conventional administration of Mitomycin C (MMC) in intravesical instillations has its limitations. In this study, MMC was loaded onto an in situ forming depot consisting of chitosan (CS), β-glycerophosphate (GP) and Fe₃O₄ magnetic nanoparticles (Fe₃O₄-MNPs) to improve its effects. The features and effects of this new drug delivery mode were investigated. The new drug delivery system (Fe₃O₄-MMC-CS/GP) exhibited superior sol-gel transformation and magnetism. Sustained release of MMC was observed both in vitro and in vivo, and the retention, which lasted for 72 h in the rat bladder, was further examined using frozen sections. The Cell-Counting Kit-8 (CCK-8) and flow cytometry assays revealed better anti-tumor activity of Fe₃O₄-MMC-CS/GP compared with the free MMC solution. Animal experiments showed that Fe₃O₄-MMC-CS/GP provided a favorable survival rate and inhibited the growth of bladder tumors. Moreover, this drug delivery system enhanced tumor cell apoptosis compared with the conventional route of MMC administration in rats.