Bajoria R, Contractor S F
Academic Department of Obstetrics and Gynaecology, Charing Cross and Westminster Medical School, London, United Kingdom.
Pediatr Res. 1997 Oct;42(4):520-7. doi: 10.1203/00006450-199710000-00017.
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.
我们旨在研究在灌注人足月胎盘的体外模型中，小单层脂质体的表面电荷对低分子量、亲水性极性分子羧基荧光素转运和摄取的影响。通过使用等摩尔浓度的卵磷脂和胆固醇制备包封羧基荧光素的中性脂质体。分别通过添加二鲸蜡酰胆碱和硬脂胺制备阴离子脂质体和阳离子脂质体。测定脂质体在血液培养基中的大小分布、包封效率和稳定性。在人足月胎盘的双灌注分离小叶中研究游离羧基荧光素和脂质体包封的羧基荧光素的转移动力学。通过荧光法测量羧基荧光素的浓度。游离羧基荧光素的母体到胎儿的转运和胎盘摄取分别为初始剂量的1.6±0.1%和4.2±0.1%。这构成对照数据。中性脂质体（2.5±0.1%；p<0.01）和阴离子脂质体（3.1±0.2%；p<0.001）显著增加了羧基荧光素的胎盘转运，而阳离子脂质体则阻止了其转运（0.4±0.1%；p<0.001）。中性脂质体（14.9±2.3%；p<0.001）和阴离子脂质体（21.1±1.2%；p<0.001）的胎盘摄取显著高于阳离子脂质体（2.3±0.6%）和对照组（p<OO1）。阳离子脂质体的胎盘摄取与对照数据相当。这些结果表明，小单层脂质体的胎盘摄取取决于其表面电荷，阴离子脂质体增强了羧基荧光素的转运，而阳离子脂质体则阻碍了其转运。
