Receptor Mobility Increases Internalization of Vasopressin In Injured Endothelial Cells

Rico C. Gunawan and Debra T. Auguste. School of Engineering and Applied Sciences, Harvard University, 40 Oxford St., ESL Rm. 224, Cambridge, MA 02138

Targeted drug delivery to inflamed vascular endothelial cells will provide a precise and effective treatment for a range of therapeutic applications. We have explored the use of liposomes to target the delivery of vasopressin to injured endothelial cells during hemorrhagic shock. Liposomes are modified with different ratios of two antibodies against intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1), which are upregulated in inflamed endothelial cells. Liposome uptake by human umbilical vein endothelial cells (HUVEC), exposed with interleukin-1 to induce inflammatory events, reaches a maximum at an equal molar ratio of ICAM-1 to ELAM-1. In comparison, the uptake of poly(lactic-co-glycolic acid) (PLGA) tagged with similar molar ICAM-1/ELAM-1 ratios is significantly lower and relatively equal at all ICAM-1/ELAM-1 ratios. This result suggests that receptor mobility plays a key role in increasing cellular uptake. We have created an in vitro coculture model to show that site-specific delivery of vasopressin to injured endothelial cells induces aligned smooth muscle cells to contract simulating blood vessel constriction.