Enhanced in vivo antitumor efficacy of fenretinide encapsulated in polymeric micelles.

Fenretinide (N-(4-hydroxyphenyl)retinamide, 4-HPR) is a synthetic retinoid with high antitumor activity against a variety of malignant cells in vitro, and is a promising candidate for cancer chemoprevention and chemotherapy. To enhance the antitumor efficacy of 4-HPR in vivo, 4-HPR were encapsulated into polymeric micelles for tumor targeting by enhanced permeability and retention effects. 4-HPR encapsulated in poly(ethylene glycol)-poly(benzyl aspartate) block copolymer micelles were prepared by the evaporation method. The mean particle size of 4-HPR encapsulated in polymeric micelles was about 173 nm. After intravenous injection into tumor-bearing mice, the delivery of 4-HPR by polymeric micelles increased the blood concentration and enhanced the tumor accumulation of 4-HPR over the injection of the 4-HPR encapsulated in oil-in-water (O/W) emulsions. Tumor growth was significantly delayed following treatment by 4-HPR encapsulated in polymeric micelles, which demonstrated the improved in vivo antitumor efficacy of 4-HPR. In addition, 4-HPR encapsulated in polymeric micelles did not cause any body weight loss. These results suggest that polymeric micelles are a promising and effective carrier of 4-HPR in order to enhance tumor delivery and have potential application in the treatment of solid tumor.