Preclinical Evaluation of Intravesical Cisplatin Nanoparticles for Non–Muscle-Invasive Bladder Cancer

Menée sur une lignée cellulaire de cancer de la vessie et à l'aide de modèles murins, cette étude analyse l'efficacité de nanoparticules polymères, chargées en cisplatine et délivrées par voie intravésicale, pour traiter un cancer non invasif de la vessie

Résumé en anglais

Purpose : Prior clinical trials evaluating cisplatin for non–muscle-invasive bladder cancer (NMIBC) were stopped due to local and systemic toxicity. Currently, there is still a need for improved intravesical therapies, and nanoparticle-based CDDP may be efficacious without the toxicity of free cisplatin observed in the past.

Experimental Design : Cisplatin nanoparticles (CDDP NPs) were developed using biocompatible poly(l-aspartic acid sodium salt; PAA), both with and without low and high grafting density of methoxy-polyethylene glycol (PEG). In vitro cytotoxicity studies confirmed activity of CDDP NPs and CDDP solution against a papillary bladder cancer cell line. Local toxicity was assessed by three weekly intravesical administrations of CDDP formulations. CDDP NPs and CDDP solution were evaluated for bladder absorption in murine models 1 and 4 hours after intravesical administration. In vivo efficacy was evaluated in an immunocompetent carcinogen model of NMIBC.

Results : CDDP NPs showed decreased local toxicity, as assessed by bladder weight, compared with CDDP solution. Furthermore, >2