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Liposomal Thyroxine: A Noninvasive Model for Transplacental Fetal Therapy¹

Academic Department of Obstetrics and Gynecology, Charring Cross and Westminster Medical School (R.B., S.F.C.); and Institute of Obstetrics and Gynecology, Royal Postgraduate Medical School, Queen Charlotte’s and Chelsea Hospital (R.B., N.M.F.), London, United Kingdom

Address all correspondence and requests for reprints to: Dr. Rekha Bajoria, Ph.D., MRCOG, Academic Department of Obstetrics and Gynecology, St. Mary’s Hospital, Research Floor, The University of Manchester Medical School, Whitworth Park, Manchester, M13 OJH, United Kingdom. E-mail: rbajoria{at}rpms.ac.uk

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 T₄ in an in vitro model of perfused human term placenta. T₄-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 T₄ were studied in a dually perfused isolated lobule of human term placenta, with creatinine and liposomal carboxyfluorescein as marker substances. Concentrations of T₄ and rT₃ were measured by RIA. T₄ crossed the placenta sparingly (1.9 ± 0.5%) because it was metabolized to rT₃ (9.2 ± 1.3%). Transplacental transfer of T₄ 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 rT₃ 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 T₄. If confirmed in vivo, liposomes may provide an alternative noninvasive method of drug delivery to the fetus.