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TitlePhysical characterization of synthetic phosphatidylinositol dimannosides and analogues in binary systems with phosphatidylcholine
Publication TypeJournal Article
Year of Publication2014
AuthorsHubert, M., Larsen D.S., Hayman C.M., Rades T., and Hook S.
JournalMolecular Pharmaceutics
Volume11
Issue3
Pagination913 - 921
Date Published2014
ISSN15438384 (ISSN)
Keywordsantigen antibody reaction, article, cell membrane, chemistry, Chemistry, Pharmaceutical, concanavalin A, controlled study, Electrophoretic mobility, lectin, Lectins, lipid monolayer, liposomal delivery, liposome, Liposomes, mannoside, Medicinal chemistry, metabolism, molecular stability, nonhuman, ovalbumin, phase transition, Phosphatidylcholine, Phosphatidylcholines, phosphatidylglycerol, phosphatidylglycerol dimannoside, Phosphatidylglycerols, Phosphatidylinositol, phosphatidylinositol dimannoside, Phosphatidylinositols, physical chemistry, priority journal, Protein Multimerization, unclassified drug, Zeta potential
AbstractNative phosphatidylinositol mannosides (PIMs) from the cell wall of Mycobacterium bovis (M. bovis) and synthetic analogues have been identified to exert immunostimulatory activities. These activities have been investigated using particulate delivery systems containing native mannosylated lipids or total lipid extracts. Limited work has been carried out examining the incorporation of individual PIM lipids into suitable particulate formulations such as liposomes. The present study explored the possibility of constructing phosphatidylcholine (PC)-based liposomes containing synthetic PIM analogues. A series of six phosphatidylinositol dimannosides (PIM2s) and phosphatidylglycerol dimannosides (PGM2s) was characterized in this study. Binary Langmuir monolayers are a useful approach for establishing pharmaceutical properties, such as lipid-lipid interactions in mixed monolayers, to facilitate the design of liposome-based delivery systems. In mixed films the phosphoglycolipids were found to be miscible with PC based on evaluation of collapse pressures and deviations of experimental molecular areas from calculated ideal values. Concanavalin A (ConA) agglutination confirmed the presence of mannosylated lipids on the surface of the liposomes. Physicochemical properties of liposomes were affected by the presence of 2% (w/w) of phosphoglycolipids with liposome stability being increased by incorporation of long-chain PIM2 and PGM2. Overall, while membrane stability of the liposomes was found to be dependent on incorporation of the phosphoglycolipids, all formulations retained proteins in amounts making them suitable for delivery. © 2014 American Chemical Society.
URLhttp://www.scopus.com/inward/record.url?eid=2-s2.0-84901742841&partnerID=40&md5=328d002f428aa7e366c0c167750b0656
DOI10.1021/mp400588y

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