Electro-kinetically assisted liposomal drug delivery system for characterization of ex-vivo cell-drug interactions
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Electro-kinetically assisted liposomal drug delivery system for characterization of ex-vivo cell-drug interactions Rajeshwari Taruvai Kalyana Kumar*, Andi Wangzhou†, David Kinnamon† and Shalini Prasad Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080
ABSTRACT This work presents a strategy to perform ex-vivo cell-drug interaction studies through electrokinetically assisted drug delivery system. Here, we present a novel technique to electrokinetically control the vesicles carrying drug to deliver to pre-determined locations. In order to achieve efficient targeted drug delivery, effect of electrokinetic attractive and repulsive forces on liposomes and target cells were studied and presented. The device consists of a simple bifurcated microfluidic chamber and microelectrodes that assist in carrying the liposomes to the target location. To test the prototype, fully grown human embryonic kidney cell lines (HEK 293) and trypsin as test drug was used. External electrical signal with voltages less than of 5 V peak-topeak (Vpp) for cells and 10 Vpp for liposomes were applied over a spectrum of frequencies to study the effect of electrokinetic forces. Through this label-free method, we were able to study loading and unloading efficiency of the drug without altering the natural properties of the liposomes and target cells. In this study, characterization and performance comparison studies for two different types of materials (HEK cells and liposomes) were performed. We were able to achieve an overall efficiency of approximately 85%. Various electrical parameters such as applied voltage, frequency and conductivity were manipulated to study the drug-cell interaction. This electrokinetic based method will be highly applicable in understanding the effect on drugs on cell populations ex vivo.
INTRODUCTION Recently several studies have been focused on developing new materials for drug entrapment and delivery which includes the use of liposomes and other bilayer formed vesicles [1]. The artificial bilayer formation also known as liposomes aim at improvement of drug loading and release efficiency, making it more suitable as well as reproducible platform for drug delivery [2]. In order to understand the efficient delivery of drug and drug-cell interaction, material of the drug and the drug carrying vesicles play a vital role [3]. To study these processes, current drug delivery methods involve the use of biomarker tags and optical techniques to guide the flow of drug carrying vesicles to the target position [4]. Here we present a novel approach to study the drug-cell interactions incorporating electrokinetic and microfluidics techniques. This label-free technique extends high resolution in implementing drug delivery system. Studies on cell interactions with specific drugs require extensive characterization to choose material for effective drug delivery for ex-vivo studies [5]. The analysis of inherent properties of the biomaterials used for delivering biochemical compounds is critical for understandin
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