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.
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Tomoyuki
T
Okuda
Shigeru
S
Kawakami
Yuriko
Y
Higuchi
Taku
T
Satoh
Yoshimi
Y
Oka
Masayuki
M
Yokoyama
Fumiyoshi
F
Yamashita
Mitsuru
M
Hashida
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000737:chemistry; D017313:Fenretinide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D010316:Particle Size; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
D004655:Emulsions; D008823:Micelles; D010455:Peptides; D011108:Polymers; D017313:Fenretinide; C033141:poly-beta-benzyl-aspartate; D011092:Polyethylene Glycols