Exploitation of Pressurised Gyration as an Innovative Manufacturing Route for Nanofibrous Structures

人们对开发由超薄纤维网状物组成的纳米纤维系统有相当大的兴趣，用于几个关键的工业应用，例如制药。简而言之，这种系统允许非常有利的物理特性，例如高表面积与体积比，这反过来又允许快速药物释放。然而，这种方法的一个主要障碍是以现实规模生产这种系统的可能性。例如，像电纺这样成熟的技术通常只能在一小时内生产出克量的材料。我们的建议是，通过使用伦敦大学学院开发的压力回转技术，我们将能够快速生产公斤数量的药物或活性负载纳米纤维，从而使此类材料的使用在商业上可行。这种方法基本上是由一个圆柱体组成，圆柱体的中轴周围有一排孔。通过在压力下施加气体并快速旋转系统，可以在环境温度下从孔中挤出聚合物溶液，同时将溶剂赶走，在周围的收集板上产生纳米纤维。我们将通过制造更高端和更强大的制造设备来进一步扩大加压回转工艺的能力。我们还将更详细地研究过程的物理，以便能够对过程进行控制并预测产品的输出特性。我们已经证明，该技术可以生产如此数量的卸载材料，因此，建议该方法可用于与药物相关的系统是完全合理的。我们计划使用三个重要且定义明确的应用程序领域来演示和探索该方法的实用性。首先，我们将研究负载细颗粒的聚合物纤维，以便我们能够开发出利用加压旋转来制造生物活性支架、石墨烯前体(通过负载石墨烯的聚合物网)、抗菌纤维绷带/口罩等的能力。其次，我们将研究难于溶于水的口服药物的配方。这是制药业的一个主要问题，因为药物在通过胃肠道吸收之前必须溶解。众所周知，将这些药物分散在聚合物中可能会提高溶解速度；我们认为，由于网状物的多孔性和这种系统的非常高的表面积，纳米纤维将更加有效。第三，我们认为这种方法可以作为冷冻干燥的替代方法，即蛋白质以固体的形式制备，在注射之前可以很容易地在添加水的溶剂中进行重组，这一过程对蛋白质来说是昂贵的和物理和化学上的创伤。因此，如果我们能够证明压力回转技术也能产生稳定、坚实和易于重组的物理形式，那么对注射剂的制药生产的影响将是相当大的。通过探索这三个应用，我们不仅将发展有关系统的赛前知识，而且我们还将把压力回转技术引入工业领域。特别是，我们将与阿斯特拉捷利康合作，他们在开发非传统药物剂型方面拥有相当的专业知识和兴趣，以适应其药物产品的要求；该公司将与学术合作伙伴密切合作，就适用性和扩大潜力提供建议。

There has been considerable interest in developing nanofibrous systems, composed of meshes of ultra-thin fibres, for usage in several key industrial applications, for example in pharmacy. In brief, such systems allow very favourable physical characteristics such as a high surface area to volume ratio which in turn allows rapid drug release. However, a major obstacle to such approaches is the possibility of producing such systems at a realistic scale. For example, well established techniques such as electrospinning can only generally produce gram quantities of material in an hour. Our proposal is that by using a pressure gyration technique developed at UCL we will be able to rapidly produce drug or active-loaded nanofibres in kilogram quantities, thereby rendering the use of such materials commercially feasible. The method basically consists of a cylinder with a bank of holes around its middle axis. By applying gas under pressure and rotating the system rapidly, it is possible to extrude a solution of the polymer from the holes under ambient temperatures, with the solvent being driven off to produce nanofibres on a surrounding collecting plate. We will expand further the capabilities of the pressurised gyration process by building a more upmarket and powerful manufacturing device. We will also study the physics of the process in greater detail in order to be able to process control and predict the output characteristics of the products. We have already demonstrated that the technique can produce such quantities of unloaded material, hence it is entirely reasonable to suggest that the approach can be used for pharmaceutically relevant systems. We plan to demonstrate and explore the utility of the approach using three important and well-defined application areas. Firstly, we will study polymeric fibres loaded with fine particulates so that we can develop capability to use pressurised gyration to manufacture bioactive scaffolds, graphene precursors (via graphene oxide-loaded polymeric meshes), antibacterial fibrous bandages/masks etc. Secondly, we will look at the formulation of poorly water-soluble drugs for oral administration. This is a major problem for the pharmaceutical industry, as a drug must dissolve before it is absorbed through the gastrointestinal tract. It is known that dispersing such drugs in polymers may enhance that dissolution rate; we argue that the nanofibres will be even more effective due to the porous nature of the mesh and the very high surface area of such a system. Thirdly, we suggest that this method may be used as an alternative to freeze drying, whereby proteins are prepared in a solid form that may be easily reconstituted prior to injection on addition of aqueous solvent, a process that is expensive and physically and chemically traumatic for the protein. Hence if we are able to show that the pressure gyration technique also produces a stable, solid and easily reconstituted physical form then the implications for pharmaceutical production of injections would be considerable. By exploring these three application we will not only develop pre-competitive knowledge regarding the systems in question but we would also be introducing the pressure gyration technique into the industrial arena. In particular, we will be working with Astra Zeneca who have considerable expertise and interest in developing non-conventional pharmaceutical dosage forms to suit the requirements of their drug products; the company will work closely with the academic partners to advise on applicability and scale-up potential.