Bajoria R, Contractor S F
Department of Obstetrics and Gynaecology, Charing Cross & Westminster Medical School, London, UK.
J Pharm Pharmacol. 1997 Jul;49(7):675-81. doi: 10.1111/j.2042-7158.1997.tb06091.x.
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.
已测定脂质体大小对低分子量、亲水性极性分子羧基荧光素经灌注人足月胎盘摄取和转运的影响。由等摩尔浓度的卵磷脂和胆固醇制备了三种不同大小的包裹羧基荧光素的中性脂质体。测定了脂质体在血基介质中的大小分布、包封效率和稳定性。采用分光光度法测定羧基荧光素的浓度。游离羧基荧光素（对照数据）的经胎盘转运和胎盘摄取分别为初始剂量的1.9±0.2%和5.0±0.7%。小脂质体显著增加了羧基荧光素的胎盘摄取和胎儿浓度（P<0.05），而大脂质体（0.82±0.13%；P<0.05）和多层脂质体（0.32±0.11%）则降低了其胎盘摄取和胎儿浓度。脂质体大小与经胎盘转运（y = -0.53 + 0.9x；r = 0.96；P<0.001；n = 24）以及羧基荧光素的胎盘摄取（y = -5.9 + 6.5x；r = 0.84；P<0.001；n = 24）之间呈负相关。该研究表明，脂质体包裹的羧基荧光素的胎盘摄取和转运速率取决于脂质体的大小。
