Yu H Y, Lin C Y
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, ROC.
J Formos Med Assoc. 1997 Jun;96(6):409-13.
The influences of liposomal surface charge on hepatic uptake of liposomes in vivo and in vitro were studied in rats. 3H-inulin was entrapped in positively charged, negatively charged or neutral liposomes composed of phosphatidylcholine, cholesterol, and a charge lipid at a molar ratio of 4:4:1, or without a charge lipid. Plasma and liver concentrations of inulin were measured 5, 15, 30, and 60 minutes after an intravenous bolus dose of liposome. The in vitro study comprised incubation of liposomes with primary culture of isolated rat hepatocytes. The incubation was terminated at 30, 60, 90, 120, and 180 minutes, and cellular uptake of inulin was determined. The results showed that the positively charged liposomes resulted in the highest plasma liposome concentration. The negatively charged liposomes gave the highest liver liposome concentration, among the three liposomes. In vitro study also demonstrated that cellular uptake of a negatively charged liposome was higher than positively charged or neutral liposomes. These results suggest that positively charged liposomes might be preferable for maintaining higher plasma concentrations, while negatively charged liposomes might be more efficient for drug delivery to the liver.
在大鼠体内和体外研究了脂质体表面电荷对脂质体肝脏摄取的影响。将3H-菊粉包封于由磷脂酰胆碱、胆固醇和一种电荷脂质以4:4:1摩尔比组成的带正电荷、带负电荷或中性脂质体中，或不含电荷脂质。静脉推注脂质体后5、15、30和60分钟测量血浆和肝脏中菊粉的浓度。体外研究包括脂质体与分离的大鼠原代肝细胞培养物的孵育。孵育在30、60、90、120和180分钟时终止，并测定细胞对菊粉的摄取。结果表明，带正电荷的脂质体导致血浆脂质体浓度最高。在三种脂质体中，带负电荷的脂质体肝脏脂质体浓度最高。体外研究还表明，带负电荷的脂质体的细胞摄取高于带正电荷或中性脂质体。这些结果表明，带正电荷的脂质体可能更有利于维持较高的血浆浓度，而带负电荷的脂质体可能在药物向肝脏递送方面更有效。
