Department of Pharmaceutics and Biopharmaceutics, Philipps Universität Marburg, 35037 Marburg, Germany.
Department of Pharmaceutics and Biopharmaceutics, Philipps Universität Marburg, 35037 Marburg, Germany; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Int J Pharm. 2021 Nov 20;609:121195. doi: 10.1016/j.ijpharm.2021.121195. Epub 2021 Oct 18.
The potent photodynamic properties of Hypericin (Hyp) elicit a range of light-dose-dependent anti-tumor activities. However, its low water solubility hampers its broad application. Therefore, the administration of Hyp into biological systems requires drug carriers that would enable sufficient bioavailability. Stimuli-triggered nanocarriers, which are sensitive to endogenous or exogenous stimuli, have become an attractive replacement for conventional therapeutic regimens. Herein, we produced optimized Hyp thermosensitive liposomes (Hyp-TSL), self-assembled from DPPC, DSPC, DSPE-PEG2000. Hyp-TSL displayed a hydrodynamic diameter below 100 nm with an adequate encapsulation efficiency of 94.5 % and good colloidal stability. Hyp-TSL exhibited thermal sensitivity over a narrow range with a phase transition temperature of 41.1 °C, in which liposomal destruction was evident in AFM images after elevated temperature above the phase transition temperature. The uptake of TSL-Hyp into MDA-MB-231 cells was significantly increased with hyperthermic treatment of 42 °C when compared to the uptake at a average physiological temperature of 37 °C. Consequent enhancement of cellular reactive oxygen species was observed after hyperthermic treatment at 42 °C. The half-maximal inhibitory concentration of Hyp TSL was reduced by 3.8 fold after hyperthermic treatment at 42 °C in comparison to treatment at 37 °C. Hyp-TSL were considered safe for intravenous applications as compared by hemocompatibility studies, where coagulation time was <50 s and hemolytic potential was <10%. Conclusively, the enhancement in tumor drug availability correlated with improved therapeutic outcomes.
金丝桃素（Hyp）具有很强的光动力特性，可引发一系列光剂量依赖性抗肿瘤活性。然而，其低水溶性限制了其广泛应用。因此，Hyp 进入生物系统需要药物载体，以实现足够的生物利用度。对内源性或外源性刺激敏感的刺激触发型纳米载体已成为传统治疗方案的一种有吸引力的替代品。在此，我们制备了优化的金丝桃素热敏脂质体（Hyp-TSL），由 DPPC、DSPC 和 DSPE-PEG2000 自组装而成。Hyp-TSL 的水动力学直径小于 100nm，包封效率为 94.5%，胶体稳定性良好。Hyp-TSL 表现出窄范围内的热敏感性，相变温度为 41.1°C，在高于相变温度的升高温度下，AFM 图像中显示出脂质体的破坏。与在平均生理温度 37°C 时的摄取相比，在 42°C 的热疗处理下，MDA-MB-231 细胞对 TSL-Hyp 的摄取显著增加。在 42°C 的热疗处理后，观察到细胞内活性氧的显著增加。与在 37°C 处理相比，在 42°C 热疗处理后 Hyp TSL 的半最大抑制浓度降低了 3.8 倍。与血液相容性研究相比，Hyp-TSL 被认为可安全用于静脉应用，其中凝血时间<50s，溶血潜力<10%。总之，肿瘤药物可用性的提高与治疗效果的改善相关。
