Cationic core-shell nanoparticles for intravesical chemotherapy in tumor-induced rat model: safety and efficacy

Abstract

Mitomycin C (MMC) has shown potent efficacy against a wide spectrum of cancers and is clinical first choice in superficial bladder tumors. However, intravesical chemotherapy with MMC has been ineffective due to periodical discharge of the bladder and instability of this drug in acidic pH, both resulting in high rate of tumor recurrence and insufficiency to prevent progression. Nanocarriers may be a promising alternative for prolonged, effective and safe intravesical drug delivery due to their favorable size, surface properties and optimum interaction with mucosal layer of the bladder wall. Hence, the aim of this study was to evaluate and optimize cationic core-shell nanoparticles formulations (based on chitosan (CS) and poly-ϵ-caprolactone (PCL)) in terms of antitumor efficacy after intravesical administration in bladder tumor induced rat model. Antitumor efficacy was determined through the parameters of survival rate and nanoparticle penetration into the bladder tissue. Safety of the formulations were evaluated by histopathological evaluation of bladder tissue as well as observation of animals treated with MMC bound to nanoparticles. Results indicated that chitosan coated poly-ϵ-caprolactone (CS-PCL) nanoparticles presented the longest survival rate among all treatment groups as evaluated by Kaplan-Meier plotting. Histopathological evaluation revealed that cationic nanoparticles were localized and accumulated in the bladder tissue. As intravesical chemotherapy is a local therapy, no MMC was quantified in blood after intravesical instillation indicating no systemic uptake for the drug which could have subsequently led to side effects. In conclusion, core-shell type cationic nanoparticles may be effective tools for the intravesical chemotherapy of recurrent bladder tumors.

Keywords: Bladder cancer; Cationic nanoparticles; Chitosan; Core-shell; Mitomycin C; Poly-ϵ-caprolactone.