title: Influence of surface coverage with poly(ethylene oxide) on attachment of sterically stabilized microspheres to rat Kupffer cells in vitro.
abstract: The attachment to rat Kupffer cells of polymeric microspheres, sterically stabilized with different amounts of pendant poly(ethylene oxide) (PEO), was assessed in vitro. Four types of copolymer polystyrene (PS) microspheres were synthesized by variation of four possible monomer ratios that included styrene, methoxy-PEO-methacrylate (750 and 2000 mol. wt PEO) and allylurea. This produced poly(styrene-(methoxy-PEO)methacrylate) microspheres with hydrophilic side-groups of either urea (PS-U-PEO) and/or mixed molecular weight (750/2000 mol. wt) PEO (PS-U-M-PEO, PS-M-PEO), or single molecular weight (2000) PEO (PS-PEO) at their surfaces. The hypothesis was tested that increasing the total content of PEO comprising the steric barrier reduces attachment to cell surfaces. Attachment of PEO microspheres bearing the urea spacer and/or mixed molecular weight PEO was found to be intermediate between charge stabilized control PS and PEO (2000 mol. wt) bearing particles. Post-adsorption of different Poloxamer (PEO-poly(propylene oxide)-PEO) surfactants to the microspheres further decreased attachment. Significant negative linear correlations between surface PEO content, measured by electron spectroscopy for chemical analysis (ESCA), and attachment to Kupffer cells were demonstrated. Decreases in attachment also resulted with all graft PEO particles bearing adsorbed sodium dodecyl sulphate (SDS), whilst the attachment of SDS-treated PS control particles increased. It is proposed that trains of adsorbed graft PEO are displaced by the SDS to increase the effective fraction of graft PEO within the steric layer. Overall, increasing the amount of hydrophilic PEO in the steric layer, from graft and adsorbed sources, reduces the attachment of these particles to Kupffer cells in vitro.
authors.affiliation: Department of Pharmaceutical Sciences, Nottingham University, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Harper
authors.forename: S S
authors.initials: SS
authors.lastname: Davis
authors.forename: M C
authors.initials: MC
authors.lastname: Davies
authors.forename: M E
authors.initials: ME
authors.lastname: Norman
authors.forename: T F
authors.initials: TF
authors.lastname: Tadros
authors.forename: D C
authors.initials: DC
authors.lastname: Taylor
authors.forename: M P
authors.initials: MP
authors.lastname: Irving
authors.forename: J A
authors.initials: JA
authors.lastname: Waters
authors.forename: J F
authors.initials: JF
authors.lastname: Watts
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D004577:Electron Probe Microanalysis; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000166:cytology; D008689:Methacrylates / Q000378:metabolism / Q000494:pharmacology; D008863:Microspheres; D008970:Molecular Weight; D011060:Poloxalene / Q000378:metabolism; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology*; D011108:Polymers; D011137:Polystyrenes / Q000378:metabolism; D051381:Rats; D012967:Sodium Dodecyl Sulfate / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
chemical_list: D008689:Methacrylates; D011108:Polymers; D011137:Polystyrenes; C095407:2-propenylurea; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols; D014508:Urea; D011060:Poloxalene