title: Phospholipid imprinted polymers as selective endotoxin scavengers.
abstract: Herein we explore phospholipid imprinting as a means to design receptors for complex glycolipids comprising the toxic lipopolysaccharide endotoxin. A series of polymerizable bis-imidazolium and urea hosts were evaluated as cationic and neutral hosts for phosphates and phosphonates, the latter used as mimics of the phospholipid head groups. The bis-imidazolium hosts interacted with the guests in a cooperative manner leading to the presence of tight and well defined 1:2 ternary complexes. Optimized monomer combinations were subsequently used for imprinting of phosphatidic acid as an endotoxin dummy template. Presence of the aforementioned ternary complexes during polymerization resulted in imprinting of lipid dimers - the latter believed to crudely mimic the endotoxin Lipid A motif. The polymers were characterized with respect to template rebinding, binding affinity, capacity and common structural properties, leading to the identification of polymers which were thereafter subjected to an industrially validated endotoxin removal test. Two of the polymers were capable of removing endotoxin down to levels well below the accepted threshold (0.005 EU/mg API) in pharmaceutical production.
authors.affiliation: Faculty of Chemistry, Technical University of Dortmund, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Sulc
authors.affiliation: Faculty of Chemistry, Technical University of Dortmund, Germany.|Hovione FarmaCiencia SA, R&D, Lisbon, Portugal.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Szekely
authors.affiliation: Faculty of Chemistry, Technical University of Dortmund, Germany.|Department of Biomedical Sciences, Faculty of Health and Society, Malmö University, Malmö, Sweden.
authors.forename: Sudhirkumar
authors.initials: S
authors.lastname: Shinde
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Society, Malmö University, Malmö, Sweden.
authors.forename: Celina
authors.initials: C
authors.lastname: Wierzbicka
authors.affiliation: Faculty of Chemistry, Technical University of Dortmund, Germany.
authors.forename: Filipe
authors.initials: F
authors.lastname: Vilela
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Society, Malmö University, Malmö, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Bauer
authors.affiliation: Faculty of Chemistry, Technical University of Dortmund, Germany.|Department of Biomedical Sciences, Faculty of Health and Society, Malmö University, Malmö, Sweden.
authors.forename: Börje
authors.initials: B
authors.lastname: Sellergren
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry; D004340:Drug Contamination / Q000517:prevention & control; D004731:Endotoxins / Q000737:chemistry / Q000302:isolation & purification*; D007093:Imidazoles / Q000737:chemistry; D008689:Methacrylates / Q000737:chemistry; D054802:Molecular Imprinting / Q000379:methods*; D018716:Molecular Mimicry; D063065:Organophosphonates / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D058105:Polymerization; D014508:Urea / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D004731:Endotoxins; D007093:Imidazoles; D008689:Methacrylates; D063065:Organophosphonates; D004364:Pharmaceutical Preparations; D010710:Phosphates; D010743:Phospholipids; C004919:ethylene dimethacrylate; D014508:Urea