Effect of the Size of Liposomes on the Transfer and Uptake of Carboxyfluorescein by the Perfused Human Term Placenta

The effect of the size of liposomes on the uptake and transfer of the low molecular-weight, hydrophilic and polar molecule carboxyfluorescein has been determined across the perfused human term placenta. Carboxyfluorescein-encapsulated neutral liposomes of three different sizes were prepared from equimolar concentrations of lecithin and cholesterol. Size distribution, encapsulation efficiency and stability of liposomes in blood-based media were determined. The concentration of carboxyfluorescein was measured spectrophotometrically. The transplacental transfer and placental uptake of free carboxyfluorescein (control data) were respectively 1.9 +/- 0.2 and 5.0 +/- 0.7% of initial dose. The placental uptake and foetal concentration of carboxyfluorescein were significantly increased by small liposomes (P < 0.05), and reduced by large (0.82 +/- 0.13%; P < 0.05) and multilamellar liposomes (0.32 +/- 0.11%). There was a negative correlation between liposome size and transplacental transfer (y = -0.53 + 0.9x; r = 0.96; P < 0.001; n = 24) and placental uptake of carboxyfluorescein (y = -5.9 + 6.5x; r = 0.84; P < 0.001; n = 24). The study indicates that placental uptake and transfer rate of liposomal carboxyfluorescein were dependant upon the size of liposomes.