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

大多数药物是以片剂或注射剂的形式提供的。然而，这些途径存在一些缺点，例如药物在到达血液之前就会降解，或者患者感到不适和针头焦虑，这导致了对不同治疗模式的探索。使用粉笔、薄膜或贴片等粘合设备将药物输送到口腔粘膜(口腔内的组织)或通过口腔粘膜输送药物，提供了无痛、自我给药的方法，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、疼痛皮损和真菌感染(鹅口疮)，这些疾病影响的人口比例令人惊讶。这些口腔疾病通常非常痛苦，使咀嚼和吞咽变得困难，并可能严重影响生活质量。尽管已经为皮肤开发了含药设备(例如尼古丁贴片)，但这种组织高度不透水，因此将药物输送到或穿过它和进入血液是困难和低效的。然而，口腔粘膜的渗透性比皮肤强得多，这使其成为药物直接进入口腔组织或进入循环的理想靶点，具体取决于所释放的药物类型。目前，通过口腔粘膜给药的药物很少，但口腔给药装置制造方法的进步引起了人们对这一领域的新兴趣，特别是无针药物给药。优化口腔粘膜给药极为重要。要做到这一点，最好、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特别有用的工具，并正越来越多地被用于医学研究。通过以数学方程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而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，并几乎通过计算机模拟来试验许多实验场景。重要的是，使用它们的净效果是减少了药物开发研究所需的动物实验数量。一个良好的药物输送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对健康和患病人体组织的药物输送的差异。不幸的是，目前代表口腔粘膜的数学模型还没有被开发出来。我们的目标是通过使用从人体组织获得的生物学数据来重新描述这一点，以创建一个虚拟的口腔粘膜模型，然后可以用来预测各种不同药物的药物释放结果。预计这将极大地增加可用于非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.