INFLUENCE OF SURFACE COVERAGE WITH POLY(ETHYLENE OXIDE) ON ATTACHMENT OF STERICALLY STABILIZED MICROSPHERES TO RAT KUPFFER CELLS IN-VITRO

被引:23
作者
HARPER, GR
DAVIS, SS
DAVIES, MC
NORMAN, ME
TADROS, TF
TAYLOR, DC
IRVING, MP
WATERS, JA
WATTS, JF
机构
[1] UNIV NOTTINGHAM,DEPT PHARMACEUT SCI,NOTTINGHAM NG2 7RD,ENGLAND
[2] ICI AGROCHEM,BRACKNELL RG12 GEY,BERKS,ENGLAND
[3] ICI PHARMACEUT PLC,MACCLESFIELD SK10 4TG,CHESHIRE,ENGLAND
[4] ICI PAINTS,SLOUGH SL2 5DS,BERKS,ENGLAND
[5] UNIV SURREY,DEPT MAT SCI,GUILDFORD GU2 5KH,SURREY,ENGLAND
关键词
POLY(ETHYLENE OXIDE); STERIC STABILIZATION; ELECTROPHORETIC MOBILITY; MICROSPHERES; KUPFFER CELLS; DRUG DELIVERY;
D O I
10.1016/0142-9612(95)98815-V
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页码:427 / 439
页数:13
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