Effect of surface charge of small unilamellar liposomes on uptake and transfer of carboxyfluorescein across the perfused human term placenta.

We aim to investigate the effect of surface charge of small unilamellar liposomes on transfer and uptake of a low molecular weight, hydrophilic and polar molecule carboxyfluorescein in an in vitro model of perfused human term placenta. Carboxyfluorescein-encapsulated neutral liposomes were prepared by using an equimolar concentration of lecithin and cholesterol. Anionic and cationic liposomes were prepared by adding dicetylcholine and stearylamine, respectively. Size distribution, encapsulation efficiency, and stability of liposomes in blood-based medium were determined. The transfer kinetics of free carboxyfluorescein and liposomally encapsulated carboxyfluorescein were studied in a dually perfused isolated lobule of human term placenta. The concentration of carboxyfluorescein was measured fluorometrically. The maternal to fetal transfer and placental uptake of free carboxyfluorescein was 1.6 +/- 0.1% and 4.2 +/- 0.1% of the initial dose, respectively. This constitutes the control data. The placental transfer of carboxyfluorescein was significantly increased by neutral (2.5 +/- 0.1%; p < 0.01) and anionic liposomes (3.1 +/- 0.2%; p < 0.001), whereas cationic liposomes prevented its transfer (0.4 +/- 0.1%; p < 0.001). The placental uptake of neutral (14.9 +/- 2.3%; p < 0.001) and anionic liposomes (21.1 +/- 1.2%; p < 0.001) were significantly higher than the cationic liposomes (2.3 +/- 0.6%) and control group (p < 0.001). The placental uptake of cationic liposomes was comparable with the control data. These results indicate that placental uptake of small unilamellar liposomes depends upon their surface charge, and transfer of carboxyfluorescein is enhanced by anionic and impeded by cationic liposomes.