Claw Shaped Polymeric Micelles-New Opportunities for the Pharmaceutical Sector

制药部门利用了许多分子相互作用，使有价值的药物化合物能够提供给患者。涉及水不溶性药物的一些分子相互作用的目的是使药物增溶，从而使药物能够被给予。尽管做出了所有这些努力，但仍有高达40%的已被证明具有生物活性的新化学实体在开发中失败，原因仅仅是a)它们不溶于水，b)没有合适的和生物相容的药物增溶剂。可用的材料包括低分子表面活性剂增溶剂，由于其洗涤剂的性质，它们往往会溶解细胞，因此生物相容性很差，所产生的溶液对稀释不稳定。另一方面，嵌段共聚物是很差的药物增溶剂。该提案建立在已确定生物相容(不会导致细胞溶解)的聚合物梳状表面活性剂的基础上，在表面活性剂中，含有水不溶侧基的可溶性聚合物可以通过特定的分子间作用在水介质中溶解水不溶分子。制药部门利用了一些分子相互作用，使有价值的药物化合物能够提供给患者。涉及水不溶性药物的一些分子相互作用的目的是使药物增溶，从而使药物能够被给予。尽管做出了所有这些努力，但仍有高达40%的已被证明具有生物活性的新化学实体在开发中失败，原因仅仅是a)它们不溶于水，b)没有合适的和生物相容的药物增溶剂。可用的材料包括低分子表面活性剂增溶剂，由于其洗涤剂的性质，它们往往会溶解细胞，因此生物相容性很差，所产生的溶液对稀释不稳定。另一方面，嵌段共聚物是很差的药物增溶剂。该建议建立在已确定生物相容(不会导致细胞裂解)的聚合物梳状表面活性剂的基础上，在表面活性剂中，含有水不溶侧基的可溶聚合物能够通过特定的分子间事件在水介质中溶解水不溶分子。具体地说，该提案考察了一种新的聚合物结构-爪状聚合物表面活性剂(如图所示)，其中不溶于水的分子存在于由每个爪状表面活性剂分子形成的疏水口袋中。这个疏水袋是由爪子上不同的两亲指头聚集而成的。在斯特拉斯克莱德大学，我们已经解决了合成的棘手部分，目标是合成各种聚合物两亲分子，使用新开发的高通量系统确定最佳结构，并研究爪形聚合物表面活性剂的自组装以及新聚合物与模型药物分子之间的分子相互作用。合适的候选人将接受初步的生物测试，以确定交付概念的证据。总成本=213,174英镑。这项工作满足了EPSRC生命科学接口计划的目标，并有助于理事会支持创新材料和工程研究的使命。

A number of molecular interactions have been harnessed by the pharmaceutical sector enable valuable drug compounds to be delivered to patients. Some molecular interactions involving water insoluble drugs are aimed at drug solubilisation, thus allowing the drugs to be administered. Despite all these efforts up to 40% of new chemical entities with proven biological activity still fail in development simply because a) they are insoluble in water and b) suitable and biocompatible drug solubilisers are unavailable. Available materials include low molecular weight surfactant solubilisers which have poor biocompatibility as they tend to lyse cells due precisely to their detergent nature and the resulting solutions are unstable to dilution. Block copolymer on the other hand are poor drug solubilisers. The proposal builds on work which has established that biocompatible (do not cause cell lysis) polymeric comb shapedsurfactants, in which soluble polymers bearing water insoluble pendant groups, are abto solubilise water insoluble molecules in aqueous media by specific intermolecularA number of molecular interactions have been harnessed by the pharmaceutical sector to enable valuable drug compounds to be delivered to patients. Some molecular interactions involving water insoluble drugs are aimed at drug solubilisation, thus allowing the drugs to be administered. Despite all these efforts up to 40% of new chemical entities with proven biological activity still fail in development simply because a) they are insoluble in water and b) suitable and biocompatible drug solubilisers are unavailable. Available materials include low molecular weight surfactant solubilisers which have poor biocompatibility as they tend to lyse cells due precisely to their detergent nature and the resulting solutions are unstable to dilution. Block copolymers on the other hand are poor drug solubilisers. The proposal builds on work which has established that biocompatible (do not cause cell lysis) polymeric comb shapedsurfactants, in which soluble polymers bearing water insoluble pendant groups, are able to solubilise water insoluble molecules in aqueous media by specific intermolecular events. Specifically the proposal examines a new polymer architecture - claw shaped polymeric surfactants (as shown in the Figure) in which the water insoluble molecule isheld in a hydrophobic pocket formed by each claw shaped surfactant molecule. The hydrophobic pocket will arise from the aggregation of the separate amphiphilic digits of the claw. At the University of Strathclyde, we have already worked out the tricky part of the synthesis and aim to synthesise a variety of polymeric amphiphiles, identify optimal architectures, using a newly developed high throughput system, and study the claw shaped polymeric surfactant self assembly as well as the molecular interactions between the new polymers and model drug molecules. Suitable candidates will undergo preliminary biological testing in order to establish proof of the delivery concept. Total cost = 213,174. The work fulfils the EPSRC Life Sciences Interface Programme objectives and contributes to the Council's mission to support innovative materials and engineering research.