Medway School of Science, Faculty of Engineering and Science, University of Greenwich, Chatham Maritime, Kent, UK.
J Pharm Pharmacol. 2021 Mar 6;73(3):300-309. doi: 10.1093/jpp/rgaa061.
Design and examine the effect of sirolimus-PEGylated (Stealth) liposomes for breast cancer treatment. In this study, we developed conventional and Stealth liposome nanoparticles comprising of distearoylphosphatidylcholine (DSPC) or dipalmitoyl-phosphatidylcholine (DPPC) and DSPE-MPEG-2000 lipids loaded with sirolimus as an anticancer agent. The effect of lipid grade, drug loading and incubation times were evaluated.
Particle size distribution, encapsulation efficiency of conventional and Stealth liposomes were studied followed by cytotoxicity evaluation. The cellular uptake and internal localisation of liposome formulations were investigated using confocal microscopy.
The designed Stealth liposome formulations loaded with sirolimus demonstrated an effective in vitro anticancer therapy compared with conventional liposomes while the length of the acyl chain affected the cell viability. Anticancer activity was found to be related on the drug loading amounts and incubation times. Cell internalization was observed after 5 h while significant cellular uptake of liposome was detected after 24 h with liposome particles been located in the cytoplasm round the cell nucleus. Sirolimus Stealth liposomes induced cell apoptosis.
The design and evaluation of sirolimus-loaded PEGylated liposome nanoparticles demonstrated their capacity as drug delivery carrier for the treatment of breast cancer tumours.
设计并研究西罗莫司聚乙二醇化（隐形）脂质体用于乳腺癌治疗的效果。在这项研究中，我们开发了由二硬脂酰基磷脂酰胆碱（DSPC）或二棕榈酰基磷脂酰胆碱（DPPC）和 DSPE-MPEG-2000 脂质组成的常规和隐形脂质体纳米颗粒，载有西罗莫司作为抗癌药物。评估了脂质种类、载药量和孵育时间的影响。
研究了常规和隐形脂质体的粒径分布和包封效率，随后进行了细胞毒性评估。使用共聚焦显微镜研究了脂质体制剂的细胞摄取和内部定位。
与常规脂质体相比，载有西罗莫司的设计隐形脂质体配方表现出有效的体外抗癌治疗效果，而酰基链的长度影响细胞活力。抗癌活性与药物载药量和孵育时间有关。在 5 小时后观察到细胞内化，在 24 小时后检测到明显的脂质体摄取，脂质体颗粒位于细胞核周围的细胞质中。西罗莫司隐形脂质体诱导细胞凋亡。
西罗莫司载药聚乙二醇化脂质体纳米颗粒的设计和评估表明其具有作为治疗乳腺癌肿瘤的药物传递载体的能力。
