Lactose mediated liver-targeting effect observed by ex vivo imaging technology

Two kinds of micelles containing Rhodamine B were prepared by a solvent evaporation method. One (Lac-f-micelles: lactose-free micelles) was from a Rhodamine-containing copolymer, poly(ethylene glycol)-b-poly(l-lactide-co-2,2-dihydroxylmethyl-propylene carbonate/Rhodamine) [PEG(5000)-b-P(LA(4000)-co-DHP(600)/Rhodamine)], and the other (Lac+micelles lactose-containing micelles) was from a mixture of the targeting copolymer lactose-poly(ethylene glycol)-poly (l-Lactide) [Lac-PEG(4600)-PLA(4500)] and the Rhodamine-containing copolymer PEG(5000)-b-P(LA(4000)-co-DHP(600)/Rhodamine). ESEM and DLS measurements showed that the two kinds of micelles have similar size (in the range of 60-100 nm) and size distribution. Cellular uptake studies in vitro revealed that the Lac+micelles showed stronger endocytosis ability than Lac-f-micelles in SMMC7221 human liver cancer cells, but the Lac+micelles were rarely internalized by Vero cells. The micelle solutions were administrated into mice via tail intravenous injection. Then, five visceral organs were isolated from the mice at specified time intervals and relative fluorescent intensities of the ex vivo organs and their homogenates were examined by CRI Maestro 500FL in vivo imaging system. The results showed that the Lac+micelles showed more remarkable liver-targeting effect than the Lac-f-micelles. And the liver-targeting effect could be established in ca. 12 h after tail i.v. injection.