Specific Adhesion of Biodegradable Microspheres to Cytokine Activated Endothelium Under Flow
In a variety of disease settings the expression of various endothelial cell adhesion molecules (ECAMs) appears to be increased, making these molecules attractive targets for directed drug delivery schemes. One approach is to use polymeric biodegradable microspheres bearing a mAb for an ECAM whose expression is increased. We used biotin-avidin chemistry to couple a mAb to E-selectin or ICAM-1 to microspheres made from a biotinylated poly (lactic acid) poly (ethylene glycol) (PLA-PEG-biotin) copolymer. We tested the adhesion of the resulting mAb coated biodegradable particles to human umbilical vein endothelial cells (HUVEC). We found that the mAb coated PLA-PEG-biotin microspheres show high specific adhesion to 4 hr. IL-1? activated HUVEC expressing high levels of E-selectin and ICAM-1 relative to the level of adhesion to unactivated HUVEC that express no E-selectin and a low level of ICAM-1. We also found that the adhesion was shear stress dependent. Additionally, we have found that the selectivity of anti-E-selectin coated microspheres to 4 hr. IL-1? activated HUVEC is a strong function of the concentration of anti-E-selectin used to generate the anti-E-selectin coated microspheres. These results suggest that PLA-PEG-biotin particles coated with mAbs to ECAMs could be used to selectively target drugs to endothelium present at sites of inflammation.
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:targeted drug delivery biodegradable carriers e selectin icam 1 in vitro flow assay
Date of Publication:01/01/2002