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Electrospray-Mediated Delivery of Biological Molecules into Mammalian Cells

Final Report Summary - TAYLORMED (Electrospray-Mediated Delivery of Biological Molecules into Mammalian Cells)

This partnership has been created to address the critically poor efficacy of existing treatment strategies to treat lung disease, a major health problem in the EU. The partnership involves groups from two academic partners in Ireland (NUI Maynooth and Trinity College Dublin) and one industry partner in the UK (Dolomite). The project involves research and development of a novel process involving electrospray to deliver biomolecule-based drugs into cells and tissues. Aimed primarily at lung diseases, the technology will ultimately also be applicable to other disease types and to a wide range of therapeutic and diagnostic molecules. This action represents a high level intersectoral collaboration between partners with complementary expertise in biological drug delivery (NUI Maynooth), mechanical and manufacturing engineering (Trinity College Dublin) and microfluidics technologies (Dolomite). The problem is being tackled by researching the parameters that influence electrospray generation and its ability to successfully deliver active biomolecules into cells.
The term ‘electrospray’ refers to the process where electrical charges are provided to a fluid in order to generate a very fine spray of the fluid. When subjected to an intense electric field, the fluid forms a ‘Taylor’ cone. Fluid instabilities break-up the emitted jet into a spray of charged droplets. Droplet evaporation and field-ion emission result in a fine spray of charged droplets that fly towards a counter electrode. While there are several applications of electrospray technology including mass spectrometry, chemical/biological deposition and colloid thrusters, the use of electrospray to deliver material into cells and tissues has not been widely studied. Furthermore, the fundamental processes underlying electrospray formation are poorly understood, limiting full exploitation of the potential of this phenomenon. We have developed a novel electrospray system which we have successfully used to demonstrate a novel application of delivering biological molecules into cells such that they remain functional within the cell. This technology holds substantial potential as a novel drug delivery method.
In this intersectoral action, we have increased general understanding of the physical processes involved in electrospray generation for biological applications. We have developed systems and devices for the generation of electrosprays and we have demonstrated ability of electrosprays to deliver of a wide range of biological molecules into cells and tissues. These technologies have applications in the area of diagnostics and drug delivery. We have also successfully delivered whole cells by electrospray towards applications in regenerative medicine and cell therapy.
Our project has been very successful. Staff were seconded between NUI Maynooth and Dolomite and from Dolomite to Trinity College and an engineer and a biologist were recruited to NUI Maynooth. In the early stages of the project, methods were established for visualising the sprays. This was critical to enable evaluation of spray quality and the parameters that affect these sprays. A range of biological buffers have been examined to determine if, and how, they can be electrosprayed. A wide range of clinically relevant molecules have been studied including DNA, siRNA, miRNA, proteins, small molecules and biological dyes. Novel electrospray emitters were designed and tested for different applications. The electrospray technology was transferred between the partners and used for a variety of novel applications, including novel non-biological applications such as cooling.
This project has substantially increased understanding of the electrospray process, benefiting all areas of application, and has significantly advanced the area of electrospray-mediated drug delivery with major relevance for pharmaceutical/drug delivery/medical device companies as well as patients and clinicians.