Defining drug delivery into and across the oral mucosa using a tissue engineering and mathematical modelling approach

大多数药物以片剂或注射剂的形式给药。然而，这些途径有许多缺点，如药物在到达血液之前降解或患者不适和针头焦虑，这导致寻找不同的治疗模式。使用膏药、薄膜或贴片等黏附装置将药物输送到口腔黏膜（口腔内部的组织）内或通过口腔粘膜，可提供无痛、自我给药，因此是一种有吸引力的替代方案。这些设备还可以用于治疗几种口腔疾病，如复发性溃疡、疼痛病变和真菌感染（鹅口疮），这些疾病影响的人口比例惊人地大。这些口腔疾病通常非常痛苦，使咀嚼和吞咽困难，并可能严重损害生活质量。虽然已经开发出用于皮肤的含药装置（例如尼古丁贴片），但这种组织是高度不渗透的，因此将药物输送到皮肤或通过皮肤进入血液是困难和低效的。然而，口腔黏膜的渗透性比皮肤强得多，这使其成为药物直接递送到口腔组织或进入血液循环的理想靶点，这取决于递送的药物类型。目前，很少有药物是通过口腔粘膜给药的，但口服给药装置的制造方式的进步使人们对这一领域产生了新的兴趣，特别是对无针给药。优化口腔黏膜给药是非常重要的。做到这一点的最好和最有效的方法是使用数学和计算模型。数学模型是研究生物系统的非常有用的工具，并且越来越多地用于医学研究。通过以数学方程式的形式写下生物系统的基本物理和生化过程，人们可以在计算机上快速有效地模拟这些生物过程。然后，这些数学模型可以用来测试许多不同的理论，做出预测，并通过计算机模拟试验许多实验场景。重要的是，使用它们的净效果是减少药物开发研究所需的动物实验数量。一个良好的药物传递数学模型可以通过确定以下因素来预测如何最佳地优化治疗：药物在粘膜组织中停留的时间或进入血液的速度，服用药物的频率，药物的理想化学性质以及药物在健康和患病人体组织中的传递差异。遗憾的是，目前还没有建立起能够代表口腔黏膜的数学模型。我们的目标是通过使用从人体组织中获得的生物学数据来创建虚拟口腔粘膜模型来解决这一问题，该模型可用于预测各种不同药物的药物输送结果。据设想，这将大大增加可用于无注射粘膜给药的药物数量。

Most drugs are delivered either in tablet form or by injection. However, these routes have a number of drawbacks such as drug degradation before reaching the bloodstream or patient discomfort and needle anxiety, which has led to the search for different modes of treatment. Drug delivery into or through the oral mucosa (the tissue that lines the inside of the mouth) using adhesive devices such as pastels, films or patches offers pain-free, self-administration of drugs and is therefore an attractive alternative. These devices could also be used to treat several oral diseases such as recurrent ulcers, painful lesions and fungal infections (thrush) that affect a surprisingly large proportion of the population. These oral diseases are often very painful, make chewing and swallowing difficult and can significantly impair quality of life.Although drug-containing devices have been developed for the skin (e.g., nicotine patch), this tissue is highly impermeable and so delivering drugs into or through it and into the bloodstream is difficult and inefficient. However, the oral mucosa is vastly more permeable than skin making it an ideal target for drug delivery either directly to the oral tissue or into the circulation, depending on the type of drug delivered. At present there are very few drugs that are delivered via the oral mucosa but advancement in the way in which oral drug delivery devices are manufactured has created new interest in this area, in particular for needle-free drug delivery. Optimising oral mucosal drug delivery is extremely important. The best and most efficient way to do this is to use mathematical and computational models. Mathematical models are exceptionally useful tools for studying biological systems and are being increasingly used in medical research. By writing down the underlying physical and biochemical processes of a biological system in the form of mathematical equations, one can quickly and efficiently simulate these biological processes on a computer. These mathematical models can then be used to test many different theories, make predictions and trial numerous experimental scenarios virtually by computer simulation. Importantly, the net effect of their use is to reduce the number of animal experiments needed in drug development research. A good mathematical model of drug delivery can forecast how to best optimise treatment by determining such factors as: how long the drug will stay in the mucosal tissue or how quickly it will enter the bloodstream, how often to take the drug, the ideal chemical properties of the drug and the differences between drug delivery to healthy and diseased human tissue. Unfortunately, at present, mathematical models representing the oral mucosa for this purpose have not yet been developed. Our aim is to readdress this by using biological data obtained from human tissue to create a virtual oral mucosal model that can then be used to predict drug delivery outcomes for a variety of different drugs. It is envisaged that this will dramatically increase the number of drugs that will be available for injection-free mucosal delivery.