Serum albumin is a well-known protein, acting as an intravascular transporter of hydrophobic nutrients and drugs in the blood circulatory system. We investigated the potential of using a cationic formulation of albumin (cBSA) as a delivery vehicle for intravesical delivery of cisplatin (CDDP) and docetaxel (DTX) against non-muscle-invasive bladder cancers. CDDP was loaded into the cBSA via coordination binding whereas DTX was loaded via hydrophobic interactions. The cBSA carrier prevented burst release of the loaded drugs and also enabled the loaded drugs to be readily taken in by UMUC3 bladder cancer cells. As a result, the dual drug-loaded cBSA complex exhibited enhanced killing efficacy against UMUC3 cells after 4 h-treatment in vitro as compared to the respective single drug-cBSA complex or non-cationized BSA loaded with the two drugs. Obvious synergy arising from the simultaneous delivery of the two drugs into the cells was indicated from the combination index. <i>Ex vivo</i> experiments with porcine bladder showed that cBSA, unlike BSA, attached readily onto the bladder luminal surface without causing extensive damage to the urothelium. Similarly, in <i>in vivo</i> tests with mice, instilled FITC-labeled cationic albumin showed longer retention and greater penetration into the glycosaminoglycan layer on the urothelium surface than the corresponding non-cationized albumin. Thus, our study demonstrates that cationized albumin, with its mucoadhesive property and capacity for loading multiple synergistic drugs and releasing them in a sustained manner, is potentially a promising drug carrier for intravesical chemotherapy against bladder cancer.

Cationized albumin carrier for potential synergistic chemotherapy of non-muscle-invasive bladder cancer

256th National Meeting (2018)

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