Targeted drug delivery offers several advantages with respect to conventional delivery methods including reduced side effects and lower drug doses. However, the delivery efficiency is significantly affected by the choice of the target epitopes that selectively interact with endothelial cells located in inflammatory sites. In this study we present a novel dualreceptor targeting approach to enhance the drug carrier's binding efficiency to the inflamed diseased tissue.
Dual-receptor targeted drug carriers were prepared by coating polymer microspheres with different molar ratios of antibodies against ICAM-1 (aICAM-1) and E-selectin (aEselectin). A flow chamber was used to study the interaction of the microspheres with TNF-α activated HUVECs under different flow conditions.Our experimental results shows that our dual-receptor targeted drug carriers have significantly higher binding efficacy compared to single-receptor targeted drug carriers. Moreover, we found that the optimal ratio of aICAM-1:aE-selectin for binding efficacy is 70:30. The level of adhesion of our carriers appeared to decrease with increase in wall shear stress.We conclude that the adhesion efficiency of the dual-receptor targeting system is significantly higher than the single-receptor. Moreover, the drug carrier adhesion ability can be improved by optimizing the ratio of the two receptors on the surface of the microspheres.
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