For
bladder cancer, intravesical chemo/
immunotherapy is widely used as adjuvant
therapy after surgical transurethral resection. Bacillus Calmette-Guerin (BCG) is a live attenuated Mycobacterium of the same family as
tuberculosis, that is capable of inducing a local inflammatory response upon instillation into the bladder. Intravesical
therapy with BCG has proved to be more effective in the prophylaxis and treatment of superficial
bladder tumors than most chemotherapeutic agents used for the same indication. However, compared to intravesical
chemotherapy, BCG
immunotherapy provokes more pronounced local and systemic reactions. In addition to the commonly induced granulomatous inflammatory changes in the bladder, which produce irritative symptoms, this
therapy may cause systemic side effects varying from mild malaise and
fever to, in rare instances, life-threatening or fatal
sepsis. Nanoparticles with positive surface charge and mucoadhesive properties were developed to overcome these side effects. Hence, the aim of this study was to optimize and evaluate cationic
chitosan (CS) nanoparticles encapsulating BCG in terms of antitumor efficacy after
intravesical administration in
bladder tumor, induced in rat model. It was found that nanoparticle formulations of 269-375 nm in size can be produced with 42% encapsulation efficiency. The zeta potential was positive and was suitable for
intravesical administration. Antitumor efficacy was determined over the parameters of histopathological evaluation, survival rate and mean bladder weight in comparison to treatment with commercial BCG
solution. Concerning survival rates, BCG-loaded
chitosan nanoparticles resulted in significantly longer survival than BCG commercial product (up to 86 days of survival with no systemic side effects). When compared to healthy bladder weight averages, all groups (especially BCG commercial
solution) showed higher bladder weights confirming
tumor formation. Histopathological findings confirmed antitumor activity in all treatment groups and optimum findings were observed in groups treated with CS nanoparticles encapsulating BCG. At the same time, significant nanoparticle accumulation in bladder tissues was observed especially for BCG-loaded CS group. In this study, it was clearly observed that cationic CS nanoparticles provide a significantly improved perspective in intravesical
immunotherapy of
bladder tumors.