title: Physical characterization of synthetic phosphatidylinositol dimannosides and analogues in binary systems with phosphatidylcholine.
abstract: Native 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 (PIM(2)s) and phosphatidylglycerol dimannosides (PGM(2)s) 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 PIM(2) 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.
authors.affiliation: School of Pharmacy and ‡Department of Chemistry, University of Otago , P.O. Box 56, Dunedin 9054, New Zealand.
authors.forename: Madlen
authors.initials: M
authors.lastname: Hubert
authors.forename: David S
authors.initials: DS
authors.lastname: Larsen
authors.forename: Colin M
authors.initials: CM
authors.lastname: Hayman
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Sarah
authors.initials: S
authors.lastname: Hook
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003208:Concanavalin A / Q000737:chemistry / Q000378:metabolism; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D010047:Ovalbumin / Q000737:chemistry / Q000378:metabolism; D044367:Phase Transition; D010713:Phosphatidylcholines / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry*; D055503:Protein Multimerization
chemical_list: D037102:Lectins; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010716:Phosphatidylinositols; C054977:phosphatidylinositol dimannoside; D003208:Concanavalin A; D010047:Ovalbumin
keywords: Langmuir trough technique; PIM analogues; liposomes; mixed monolayer; phosphatidylinositol dimannoside; physical characterization