Block copolymer design for stable encapsulation of N-(4-hydroxyphenyl)retinamide into polymeric micelles in mice

For stable encapsulation of N-(4-hydroxyphenyl)retinamide (4-HPR) into polymeric micelles, four types of block copolymers were synthesized with different esterified functional groups: heptyl (C7), nonyl (C9), benzyl (Bz), and phenylpropyl (C3Ph). The stability of 4-HPR encapsulated polymeric micelles was evaluated by measuring the blood concentration of 4-HPR in mice. After intravenous administration of 4-HPR and 4-HPR encapsulated PEG liposomes, the blood concentration of 4-HPR was about 2.8% and 2.2% of the dose/mL, suggesting the rapid release of 4-HPR from PEG liposomes. In contrast, the blood concentration of 4-HPR after intravenous administration of all 4-HPR encapsulated polymeric micelles studied was much higher (about 22-34% of the dose/mL). Among them, the polymeric micelles prepared by block copolymers (Bz) showed the highest blood concentration of 4-HPR. As far as the effects of the level of Bz groups in the block copolymers are concerned, the blood concentration of 4-HPR was enhanced by Bz groups at a level of 72% and 77%, but not by Bz groups at a level of 43% and 51%. These results suggest that 4-HPR is stably encapsulated in polymeric micelles prepared by block copolymers (Bz) but a level of over 72% of Bz groups is needed. These findings will be of value in the future use, design, and development of polymeric micelles for in vivo application of 4-HPR.