FENRETINIDE-LOADED NANOCARRIERS INHIBIT CELL MIGRATION, SPHEROID FORMATION AND BREAST CANCER DEVELOPMENT IN AN IN VIVO CARCINOGENESIS MODEL

The efficacy of bioresponsive fenretinide-loaded nanocarriers for breast cancer chemoprevention was assessed. Microemulsions (ME) capable of transforming into hexagonal phase in vivo upon mammary administration were prepared using phosphatidylcholine, water, propylene glycol and fenretinide (1%). Treatment with ME doses capable of reducing cell viability in 15% (IC15) for 24 h reduced breast cancer cell (T47D) migration by 4.2-fold; treatment for 5 days reduced the size (1.4-fold) of T47D spheroids compared to untreated or cell treated with unloaded ME. Fenretinide solution did not display a similar effect most likely due to drug precipitation in the medium. Using an in vivo model of MNU-induced carcinogenesis, we observed that intramammary administration of ME every 3 weeks for 3 months reduced the incidence of breast tumors by 6.7-fold compared to untreated animals. These results support the potential of fenretinide-loaded nanocarriers for use as an effective and much needed strategy for prevention of breast cancer.