Rational design of new materials for controlled drug release applications

药物控释应用新材料的合理设计

• 批准号: EP/D074762/1
• 负责人: Lev Sarkisov
• 金额: $ 24.78万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FD074762%2F1
• 关键词: Rational; design; new; materials; controlled

The efficacy of drug therapies can be increased immensely by precise control of the location and rate of the drug release. One way to control drug delivery is to store the active agent in a porous material, or a matrix, which would slowly release the medicine through its pores. This can be useful in sustaining the desired level of a medicine in the body over an extended period of time for a range of conditions such as diabetes and some forms of cancer. This approach can be even further improved if there was a way to prepare porous materials which would selectively and strongly bind the desired drug molecules, making the release time even longer. An exciting recent idea is that we can use new types of polymers for this purpose. These polymers are prepared by mixing monomers and the second component, called template. After polymerization, where monomers link with each other, the template is removed, creating cavities and channels in the polymeric structure. Since the structure of the polymer forms around the template molecules (imprinting), it is possible that many of the cavities formed are of the shape that is complementary to template molecules, like lock and key, or hand and glove. Therefore, one can hypothesize that this material should recognize and bind template molecules. In fact, this ideology is borrowed from biological systems, where the geometrical (and interaction) match between two molecular objects is called molecular recognition and plays a vital part in many processes, including enzymes functions and genetic information replication! A number of world renowned groups (Peppas and Langer in the US, Pilevsky and Turner in the UK, Mosbach in Sweden) have been developing these new polymers with desired functions.Although simple in principle, this concept is difficult to implement for controlled drug delivery. The final structure should combine selectivity (so it binds only desired molecules) and at the same time be accessible, that is the drug molecules should be able to go in and out of the structure. This is a difficult compromise to achieve and the final result depends on many experimental variables, such as components structure and concentrations, temperature and so on. Moreover, it is not even clear what this compromise should be for controlled drug delivery applications.This problem is tedious to investigate in experiments, considering a large number of possible factors. A more efficient approach is to construct a simplified model that imitates a real system and use a computer to calculate its properties. This is called computer simulation approach. Sometimes, the behaviour of the model can be reduced to several simple (or not so simple!) mathematical formulas, which we would generally call a theory.The purpose of this proposal is to construct models of possible materials for controlled drug delivery and to investigate their properties as a function of processing conditions using theory and computer simulations. This will help us understand the mechanism of molecular recognition and what features a material should have in order to exhibit this property. We will also show how this property depends on various factors involved in material synthesis and how it is interconnected with other important characteristics of the material such as accessibility and selectivity. Eventually, we aim at designing a faster, cheaper and more efficient route to synthesis of new materials for controlled drug delivery, hoping it will help to battle a range of illnesses, from arthritis to diabetes and cancer.

通过精确控制药物释放的位置和速度，可以极大地提高药物治疗的疗效。控制药物输送的一种方法是将活性物质储存在多孔材料或基质中，这将通过其毛孔缓慢释放药物。对于糖尿病和某些形式的癌症等一系列疾病，这可能有助于在较长一段时间内维持体内所需的药物水平。如果有一种方法可以制备多孔性材料，选择性地强烈结合所需的药物分子，使释放时间更长，这种方法还可以进一步改进。最近一个令人兴奋的想法是，我们可以使用新型聚合物来实现这一目的。这些聚合物是由单体和称为模板的第二组分混合而成的。聚合后，单体相互连接，模板被移除，在聚合结构中产生空腔和通道。由于聚合物的结构形成在模板分子周围(印迹)，所以形成的许多空腔的形状可能与模板分子互补，如锁和钥匙，或手和手套。因此，人们可以假设这种材料应该识别和结合模板分子。事实上，这种思想是从生物系统中借鉴而来的，在生物系统中，两个分子对象之间的几何(和相互作用)匹配被称为分子识别，并在许多过程中发挥重要作用，包括酶的功能和遗传信息复制！许多世界知名的集团(美国的Peppas和Langer，英国的Pilevsky和Turner，瑞典的Mosbach)一直在开发具有所需功能的新聚合物。尽管原理上很简单，但这个概念很难在受控药物输送中实现。最终的结构应该结合选择性(因此它只结合所需的分子)，同时可以访问，即药物分子应该能够进出结构。这是一个很难实现的妥协，最终结果取决于许多实验变量，如组分的结构和浓度、温度等。此外，对于受控药物输送应用来说，甚至还不清楚这种妥协应该是什么。考虑到大量可能的因素，这个问题在实验中调查是乏味的。一种更有效的方法是构建一个模拟真实系统的简化模型，并使用计算机计算其性质。这就是计算机模拟方法。有时，模型的行为可以简化为几个简单的(或不那么简单的！)数学公式，我们通常称之为理论。这项建议的目的是构建可能的药物控制输送材料的模型，并使用理论和计算机模拟来研究它们作为工艺条件的函数的性质。这将有助于我们理解分子识别的机制，以及材料应该具有哪些特征才能展示这种性质。我们还将展示这种特性如何依赖于材料合成中涉及的各种因素，以及它如何与材料的其他重要特性(如可访问性和选择性)相互关联。最终，我们的目标是设计一种更快、更便宜、更有效的方法来合成用于受控给药的新材料，希望它将有助于对抗从关节炎到糖尿病和癌症的一系列疾病。