Liposomal thyroxine: A noninvasive model for transplacental fetal therapy

Drugs that cross the placenta sparingly are currently given directly to the fetus by invasive procedures. We investigated whether anionic small unilamellar (SUV) liposomes of different lipid compositions enhanced the transfer and uptake of T-4 in an in vitro model of perfused human term placenta. T-4-encapsulated anionic liposomes were prepared using lecithin (F-SUV) or distearoyl phosphatidylcholine (S-SUV) with cholesterol and dicetylcholine. The size distribution, encapsulation efficiency, and stability were determined in blood-based media. The transfer kinetics of free and liposomally encapsulated T-4 were studied in a dually perfused isolated lobule of human term placenta, with creatinine and liposomal carboxyfluorescein as marker substances. Concentrations of T-4 and rT(3) were measured by RIA. T-4 crossed the placenta sparingly (1.9 +/- 0.5%) because it was metabolized to rT(3) (9.2 +/- 1.3%). Transplacental transfer of T-4 was significantly increased by F-SUV (15.8 +/- 2.1%; P < 0.001) and S-SUV liposomes (7.1 +/- 1.2%; P < 0.001), with a concomitant decrease in fetal rT(3) levels (P < 0.001). Placental uptake of F-SUV (13.5 +/- 2.0%; P < 0.001) was greater than that of S-SUV liposomes (6.7 +/- 0.8%; P < 0.001). Our data suggest that anionic Liposomes increase transplacental transfer of T-4. If confirmed in vivo, liposomes may provide an alternative noninvasive method of drug delivery to the fetus.