Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Chemistry & Biomedicine, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Future Med Chem. 2012 Nov;4(17):2205-16. doi: 10.4155/fmc.12.165.
The application of macromolecules as therapeutic agents holds great promise for several major disorders such as cancer and cardiovascular disease. However, their use is limited by the lack of efficient, safe and specific delivery strategies. A promising strategy to overcome these challenges might be the use of thiolated polymers or designated thiomers. Thiomers are synthesized by immobilization of sulfhydryl bearing ligands on a polymeric backbone of well-established polymers. These multifunctional polymeric excipients show advantages in mucoadhesion, enzyme and efflux pump inhibition in comparison to unmodified polymers. One obstacle in the use of thiomers is that they are prone to oxidation at lower pH but this could be solved by introducing a completely new generation of thiomers, namely, the preactivated thiomer generation. Preactivated thiomers are mixed disulfides, which exhibit oxidation resistance and, beyond that, improved thiomer features. This review summarizes recent findings of polymeric excipients for macromolecular drug delivery as well as their synthesis and distinctive features.
大分子作为治疗剂的应用在癌症和心血管疾病等几种主要疾病的治疗方面具有很大的前景。然而，它们的使用受到缺乏有效、安全和特定的输送策略的限制。克服这些挑战的一种有前途的策略可能是使用巯基化聚合物或指定的硫醚。硫醚是通过将含巯基的配体固定在经过充分验证的聚合物主链上来合成的。与未修饰的聚合物相比，这些多功能聚合物赋形剂在粘合力、酶和外排泵抑制方面具有优势。在使用硫醚时的一个障碍是它们在较低 pH 值下容易氧化，但通过引入新一代完全新型的硫醚，即预激活硫醚生成，这个问题可以得到解决。预激活硫醚是混合二硫键，其具有抗氧化性，除此之外，还具有改善的硫醚特性。这篇综述总结了用于大分子药物输送的聚合物赋形剂及其合成和独特特性的最新发现。
