کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9914 | 653 | 2010 | 8 صفحه PDF | دانلود رایگان |

Targeted drug delivery to inflamed or injured vascular endothelial cells (ECs) and smooth muscle cells (SMCs) may provide a precise and effective therapeutic treatment for cardiovascular diseases. Upregulation of cytokine-regulated cell surface receptors, intercellular cell adhesion molecule-1 (ICAM) and endothelial-leukocyte adhesion molecule-1 (ELAM), on ECs and SMCs are used to target drug delivery vehicles. Recent studies demonstrate clustering of these molecules in lipid rafts may affect binding due to a nonhomogenous presentation of antibodies. We hypothesized that altering the antibody ratio for ICAM and ELAM (aICAM:aELAM) and mobility would influence cellular targeting. To alter antibody mobility, liposomes were prepared from either 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC, C18:1, Tm = −20 °C) or 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC, C16:0, Tm = 42 °C) which are in the liquid crystalline (Lα) and gel phase (Lβ) at 37 °C, respectively. We report that cellular binding of DOPC immunoliposomes by ECs is maximal at an equimolar ratio of aICAM:aELAM whereas DPPC immunoliposomes showed no ratio dependence and binding was reduced by more than 2-fold. SMCs, which do not express ELAM, show a dependence on aICAM surface density. These results suggest that antibody mobility and molar ratio play a key role in increasing receptor-mediated cell targeting.
Journal: Biomaterials - Volume 31, Issue 5, February 2010, Pages 900–907