Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal.
Arch Biochem Biophys. 2021 Jun 15;704:108858. doi: 10.1016/j.abb.2021.108858. Epub 2021 Mar 30.
Success rates in drug discovery are extremely low, and the imbalance between new drugs entering clinical research and their approval is steadily widening. Among the causes of the failure of new therapeutic agents are the lack of safety and insufficient efficacy. On the other hand, timely disease diagnosis may enable an early management of the disease, generally leading to better and less costly outcomes. Several strategies have been explored to overcome the barriers for drug development and facilitate diagnosis. Using lipid membranes as platforms for drug delivery or as biosensors are promising strategies, due to their biocompatibility and unique physicochemical properties. We examine some of the lipid membrane-based strategies for drug delivery and diagnostics, including their advantages and shortcomings. Regarding synthetic lipid membrane-based strategies for drug delivery, liposomes are the archetypic example of a successful approach, already with a long period of well-succeeded clinical application. The use of lipid membrane-based structures from biological sources as drug carriers, currently under clinical evaluation, is also discussed. These biomimetic strategies can enhance the in vivo lifetime of drug and delivery system by avoiding fast clearance, consequently increasing their therapeutic window. The strategies under development using lipid membranes for diagnostic purposes are also reviewed.
药物发现的成功率极低,新药进入临床研究和获得批准之间的不平衡正在稳步扩大。新治疗药物失败的原因包括缺乏安全性和疗效不足。另一方面,及时的疾病诊断可以实现疾病的早期管理,通常会带来更好、更经济的结果。已经探索了几种策略来克服药物开发的障碍并促进诊断。使用脂质膜作为药物输送平台或生物传感器是很有前途的策略,因为它们具有生物相容性和独特的物理化学性质。我们研究了一些基于脂质膜的药物输送和诊断策略,包括它们的优点和缺点。关于基于合成脂质膜的药物输送策略,脂质体是成功方法的典型例子,已经有很长一段时间的临床应用。还讨论了正在临床评估中使用生物来源的基于脂质膜的结构作为药物载体的情况。这些仿生策略可以通过避免快速清除来延长药物和输送系统的体内寿命,从而增加其治疗窗口。还回顾了正在开发的用于诊断目的的基于脂质膜的策略。