R Bajoria1, S Sooranna, R Chatterjee. 1. Imperial College, School of Medicine, Chelsea and Westminster Hospital, London, UK; University College London, Institute for Women's Health London, UK. Electronic address: r.bajoria@ucl.ac.uk.
Abstract
INTRODUCTION: Use of drugs that cross the placenta freely are currently avoided during pregnancy. We investigated whether cationic small unilamellar (SUV) liposomes of different lipid compositions could prevent the transfer and uptake of warfarin across human term placenta. METHODS: Cationic liposomes encapsulated warfarin was prepared by using lecithin (F-SUV) or sterylamine (S-SUV) with cholesterol and stearylamine. The size distribution, encapsulation efficiency, and stability were determined in blood-based media. The transfer kinetics of free and liposomally encapsulated warfarin were studied in a dually perfused isolated lobule of human term placenta with creatinine. Concentrations of warfarin were measured by fluorimetry. Data are expressed as % of initial dose added and given as mean ± sd. RESULTS: Warfarin crossed the placenta freely (14.9 ± 1.1%). Trans placental transfer of warfarin was significantly reduced by F-SUV (6.4 ± 0.6%; P < 0.001) and S-SUV liposomes (5.0 ± 0.8%; P < 0.001). Placental uptake of F-SUV (6.3 ± 1.7%; P < 0.001) was greater than that of S-SUV liposomes (2.2 ± 0.5%; P < 0.001). CONCLUSION: Our data suggest that cationic liposomes reduce trans placental transfer of warfarin. If confirmed "in vivo", liposomes might provide an alternative non-invasive method of drug delivery to the mother.
INTRODUCTION: Use of drugs that cross the placenta freely are currently avoided during pregnancy. We investigated whether cationic small unilamellar (SUV) liposomes of different lipid compositions could prevent the transfer and uptake of warfarin across human term placenta. METHODS: Cationic liposomes encapsulated warfarin was prepared by using lecithin (F-SUV) or sterylamine (S-SUV) with cholesterol and stearylamine. The size distribution, encapsulation efficiency, and stability were determined in blood-based media. The transfer kinetics of free and liposomally encapsulated warfarin were studied in a dually perfused isolated lobule of human term placenta with creatinine. Concentrations of warfarin were measured by fluorimetry. Data are expressed as % of initial dose added and given as mean ± sd. RESULTS:Warfarin crossed the placenta freely (14.9 ± 1.1%). Trans placental transfer of warfarin was significantly reduced by F-SUV (6.4 ± 0.6%; P < 0.001) and S-SUV liposomes (5.0 ± 0.8%; P < 0.001). Placental uptake of F-SUV (6.3 ± 1.7%; P < 0.001) was greater than that of S-SUV liposomes (2.2 ± 0.5%; P < 0.001). CONCLUSION: Our data suggest that cationic liposomes reduce trans placental transfer of warfarin. If confirmed "in vivo", liposomes might provide an alternative non-invasive method of drug delivery to the mother.
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