Liposomal thyroxine : A noninvasive model for transplacental fetal therapy

• Published in: The journal of clinical endocrinology and metabolism Vol. 82; no. 10; pp. 3271 - 3277
• Main Authors: BAJORIA, R, FISK, N. M, CONTRACTOR, S. F
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.10.1997
• Subjects: Biological and medical sciences; Chromatography; Drug Carriers; Female; Fetal Diseases - drug therapy; Hormones. Endocrine system; Humans; In Vitro Techniques; Liposomes; Maternal-Fetal Exchange; Medical sciences; Pharmacology. Drug treatments; Phospholipids; Placenta - metabolism; Pregnancy; Thyroxine - administration & dosage; Thyroxine - pharmacokinetics; Human; Pregnancy disorders; Placental transfer; Aminoacid derivative hormone; Liposome; In vitro; Fetal diseases; Placenta; Perfusion; Thyroxine; Dosage form; Thyroid hormone; Models; Fetal therapy
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.82.10.3271

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.