Wagner José FÁVARO, Ana Claudia SILVA LIMA, Queila Cristina DIAS, Patrick Vianna GARCIA, Nelson DURÁN

Nanocrystal’s Formulation of Biological Response Modifier P-MAPA on Bladder Cancer Compared to Bacillus Calmette-Guerin Immunomodulator

OBJECTIVE P-MAPA (200-400 μm) is known that exhibited significant in vivo antitumor activity, unfortunately with low capacity of suspension. Our aim is to study the effects of nanocrystals (400-600 nm) produced by nanonization compared to bacillus Calmette-Guerin (BCG) vaccine on bladder cancer at a non-muscle invasive stage (NMIBC). METHODS To induce NMIBC, 20 female Fischer 344 rats received intravesically 1.5 mg/kg dose of N-methyl-N- nitrosourea (MNU), and control animals were injected with PBS solution. After cancer induction, MNU (cancer) group received identical treatment that control group; a group received 106 CFU dose of BCG for 6 weeks; P-MAPA-Nano+Pluronic group was injected with intravesically 0.8 mg/kg dose of P-MAPA for 6 weeks. A histopathological analysis of bladder after 16 weeks was carried out. Following the same procedure, the P-MAPA-Nano-Chitosan was studied. RESULTS In P-MAPA-Nano+Pluronic crystals, a better antitumor activity than BCG treatment was found and correlated with the apoptosis raised. However, unfortunately in the case of chitosan as stabilizer, the effect was negligible. One reasonable explanation to this low effect was probably through a drastic pH change (basic) in the urinary bladder in cancer case. CONCLUSION The results demonstrated that this new nanoformulation of P-MAPA in the presence of Pluronic F68 could be a potential candidate for treatment of in vivo bladder cancer.

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