脂质体是第一种成功进入临床应用，也是目前进入临床应用最多的一类纳米递药体系，将药物装载于脂质体中可以实现降低非特异性吸收、提高靶组织的富集量、降低副作用等目的。但是当前的脂质体技术仍然存在着诸多缺陷，例如载药量低以及靶向效果差等。新的脂质体载药技术的发展使得脂质体的载药量和包封率有了很大的提升。将热、激光、超声、离子辐射等外源物理刺激与脂质体药物结合可以提高脂质体药物在肿瘤的富集量，同时调节药物的释放。脂质体独特的核壳结构使得脂质体可以同时装载多种药物从而实现联合给药，通过合理设计脂质体纳米材料的结构不仅能够实现多种药物的递送，还能够实现药物的程序性释放。脂质体不仅能够装载治疗性药物，还能装载具有造影功能的组分，从而实现对治疗过程的影像监控。本文将主要介绍近五年在脂质体的载药方法、靶向给药、药物控释、联合给药、影像可视化等方面的一些重要进展。
Liposome is one of the most popular drug delivery system due to its structure similarity to cell, high biocompatibility, availability for loading various drugs(hydrophobic, hydrophilic or amphiphilic), etc. Since its first development in 1965, tremendous technical advances have been made in this field, resulting in tens of liposomal drugs applied in clinic. However, the liposomal technology is far from perfect. The defects of liposomal technology include low drug loading, insufficient tumor targeting, etc. This review focuses on some major advances in recent years in terms of drug loading, targeting delivery, controlled release, and imaging monitoring. Traditionally, the drug loading of liposome is conducted by a passive loading method, characterized with low drug loading capability, low encapsulating efficiency and high drug leaking. Although the development of pH gradient method makes some drug loaded at very high encapsulating efficiency, this method is only suitable for some ionizable drugs and the maximum drug loading capability is usually not higher than 10 wt%. The newly developed active loading procedure by ferrying hydrophobic drugs with ionizable cycolodextran makes active loading of hydrophobic drugs possible. The application of reverse-phase microemulsion enables some platinum-based drugs loaded in the liposome as a nanoprecipitate characterized with a remarkably high drug loading capability. Direct conjugating drugs onto the liposomal membrane is another promising method with high drug loading, high encapsulating efficiency and minimal drug leaking. Efficient target delivery of liposomes to tumors is critical in improving therapeutic efficacy, yet strategies involving ligand modification have been difficult to achieve in clinic. Many researches have shown that some physical methods including heat, laser, ultrasound and ionizing irradiation can not only significantly increase liposomal accumulation, but also control the drug release. This indicates that combining liposome-based therapy with some minimal-invasive physical therapy such as hyperthermia therapy, photodynamic therapy and radiation therapy would maximize the targeting ability of liposome and release the drug in a controlled manner. The unique lipid-encapsulated core-shell structure makes liposome a versatile platform for loading various drugs. The liposome can be used to co-encapsulate two or more drugs that target different pathways, thus making combination therapy possible. Compared to the single-drug therapy, the combination therapy offers several advantages including reduced dose, less drug resistance, low toxicity and improved efficacy. In addition to therapeutic agents, the liposome can also load some imaging agents, thus enabling liposome "visible". The development of "visible" liposome makes it possible to monitor in real time the behavior of liposomal drugs in vivo, which is impossible to do with conventional method. In conclusion, the liposome has witnessed many technical advances in recent years. However, to further optimize these advances and finally translate them into clinic to benefit patients, a lot more work still needs to do.
Contents
1 Introduction
2 The innovation of drug loading methods improves drug loading capability and encapsulation efficiency
3 Stimulates controlled targeted and drug released liposome
3.1 Temperature sensitive liposome
3.2 Photodynamic enhanced targeted and drug released liposome
3.3 Ultrasound controlled targeted and drug released liposome
3.4 Radio enhanced targeted and drug released liposome
4 Combination drug released liposome
5 Visualization liposome assessing therapy processes
6 Conclusion
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