a Faculty of Pharmaceutical Sciences , The University of British Columbia , Vancouver , BC , Canada.
J Drug Target. 2018 Jun-Jul;26(5-6):407-419. doi: 10.1080/1061186X.2017.1419361. Epub 2018 Jan 21.
Thermosensitive liposomes (TSLs) have been a prominent area of study in the discipline of tumour-targeted chemotherapeutics. The representative product of TSLs is ThermoDox (DPPC/lyso-PC/PEG-lipid), which has advanced to Phase III clinical trials. Various groups have sought to develop a new TSL to improve upon the LTSL (lyso-lipid temperature-sensitive liposomes) formulation that is used to prepare ThermoDOX. This review focuses on the development and recent update of an innovative TSL formulation, HaT-liposomes composed of DPPC and Brij78. Various parameters of LTSL and HaT-liposomes are compared, including size, loading efficiency, transition temperature, temperature-dependent release kinetics, stability, pharmacokinetics, biodistribution and antitumour activity. Theranostic techniques involving HaT-liposomes are reported with regard to magnetic resonance imaging of drug delivery to tumours and identification of an early therapeutic biomarker in the treated tumour. The development of a further improved TSL formulation upon HaT-liposomes with improved stability and prolonged blood circulation is reported. Delivery of membrane impermeable drugs using HaT-liposomes is explored. Finally, the challenges and future perspectives of this technology are discussed.
热敏脂质体（TSLs）一直是肿瘤靶向化疗领域的一个重要研究领域。TSLs 的代表性产品是 ThermoDox（DPPC/lysolipid/PEG-lipid），它已经进入 III 期临床试验。许多研究小组试图开发一种新的 TSL，以改进用于制备 ThermoDOX 的 LTSL（溶脂温度敏感脂质体）制剂。本文重点介绍了一种新型 TSL 制剂 HaT-liposomes 的开发和最新进展，它由 DPPC 和 Brij78 组成。比较了 LTSL 和 HaT-liposomes 的各种参数，包括粒径、载药效率、相变温度、温度依赖性释放动力学、稳定性、药代动力学、分布和抗肿瘤活性。报告了涉及 HaT-liposomes 的治疗诊断技术，包括药物向肿瘤的磁共振成像输送和治疗肿瘤中早期治疗生物标志物的识别。还报告了在 HaT-liposomes 的基础上进一步改进 TSL 制剂的开发，提高了稳定性和延长了血液循环时间。探索了使用 HaT-liposomes 输送膜不可渗透药物的方法。最后，讨论了该技术的挑战和未来前景。
