Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands.
J Control Release. 2010 Apr 19;143(2):274-9. doi: 10.1016/j.jconrel.2010.01.006. Epub 2010 Jan 13.
Liposomes are potent nanocarriers to deliver chemotherapeutic drugs to tumors. However, the inefficient drug release hinders their application. Thermosensitive liposomes (TSL) can release drugs upon heat. This study aims to identify the optimum 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG(2000) (DSPE-PEG(2000)) concentration in stealth TSL to improve content release efficiency under mild hyperthermia (HT). TSL were prepared with DSPE-PEG(2000) from 1 to 10 mol%, around 80 nm in size. Quenched carboxyfluorescein (CF) in aqueous phase represented encapsulated drugs. In vitro temperature/time-dependent CF release and TSL stability in serum were quantified by fluorometry. In vivo CF release in dorsal skin flap window chamber models implanted with human BLM melanoma was captured by confocal microscopy. In vitro heat triggered CF release increased with increasing DSPE-PEG(2000) density. However, 6 mol% and higher DSPE-PEG(2000) caused CF leakage at physiological temperature. TSL with 5 mol% DSPE-PEG(2000) were stable at 37 degrees C, while released 60% CF in 1 min and almost 100% CF in 1h at 42 degrees C. In vivo optical intravital imaging showed immediate massive CF release above 41 degrees C. In conclusion, incorporation of 5 mol% DSPE-PEG(2000) optimized stealth TSL content release triggered by HT.
脂质体是一种有效的纳米载体，可将化疗药物递送到肿瘤部位。然而，药物释放效率低下限制了其应用。热敏脂质体（TSL）可以在加热时释放药物。本研究旨在确定隐形 TSL 中最佳的 1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-聚乙二醇（2000）（DSPE-PEG（2000））浓度，以提高温和热疗（HT）下的药物内容物释放效率。使用 DSPE-PEG（2000）从 1 至 10mol%制备 TSL，粒径约为 80nm。水相中的猝灭羧基荧光素（CF）代表包封的药物。通过荧光法定量测量体外温度/时间依赖性 CF 释放和 TSL 在血清中的稳定性。通过共聚焦显微镜捕获植入人 BLM 黑色素瘤的背部皮瓣窗口室模型中的体内 CF 释放。体外热触发 CF 释放随 DSPE-PEG（2000）密度的增加而增加。然而，6mol%及更高浓度的 DSPE-PEG（2000）会导致在生理温度下 CF 泄漏。含 5mol% DSPE-PEG（2000）的 TSL 在 37°C 时稳定，而在 42°C 下 1 分钟内释放 60%CF，1 小时内几乎释放 100%CF。体内光学活体成像显示，在 41°C 以上时立即大量释放 CF。总之，在 HT 触发下，掺入 5mol% DSPE-PEG（2000）可优化隐形 TSL 的内容物释放。
