Cell-derived liposomes : targetting studies

• Main Author: Chua, Chung Tah.
• Other Authors: Subramanian Venkatraman
• Format: Final Year Project
• Language: English
• Published: 2012
• Subjects: DRNTU::Engineering::Materials::Biomaterials
• Online Access: http://hdl.handle.net/10356/48834
• Institution: Nanyang Technological University

Balloon angioplasty is a common procedure to mechanically widen a narrowed blood vessel and drug-eluting stents are used to provide mechanical support thereafter. Endothelium denudation is a common injury event after balloon angioplasty and often leads to thrombosis or restenosis. This highlights the importance of endothelium healing and current treatment involves drug delivery to cellular targets or cytokines released near sites of injury. Recent advancement in drug delivery system is the use of RGD sequence to target sites of interest. However, grafted RGD sequences on drug delivery vehicles have a short circulation half-life and this poses challenges to interaction with cells and ultimately, a lower drug release and therapeutic efficiency. In the present study, we have proposed cell-derived liposomes as the vehicle to deliver drugs to targeted extracellular matrix (ECM) near to the site of injury. Endothelium healing after balloon angioplasty is characterized with vascular smooth muscle cell proliferation in an abundance of ECM deposition. As such, the proposed cell-derived liposomes, which can recognize native ECM through the RGD sequence present on Fibronectin, offers an exciting research opportunity. The potential of this delivery system prolongs RGD targeting and can ultimately reduce frequency of dosage administration, thereby improving patient compliance. In the study, we have attachment studies, dilution studies and fluorescence imaging of HUVECs-derived liposomes on freshly cut discs of porcine aorta. We have observed increased liposome attachment when aorta discs were subjected to damage by sonication. However, the significance of this increase is not as high as expected and further studies are needed to re-affirm this finding. Further studies can be focused on the effect of high liposome concentration (>0.83 million liposomes per ml) on attachment to porcine aorta. The effect of calcium concentration can also offer a possible route of research. Ultimately, flow-through reactor system can be employed to investigate the effect of blood flow on liposome attachment as dynamic conditions in the blood vessel can pose great challenge to targeting properties.