Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China.
Department of Pharmacy, Ministry of Health Service, Chinese PLA General Hospital, Beijing, People's Republic of China.
Int J Nanomedicine. 2020 Jan 24;15:553-571. doi: 10.2147/IJN.S228715. eCollection 2020.
Breast cancer is the leading cause of cancer death in women. Chemotherapy to inhibit the proliferation of cancer cells is considered to be the most important therapeutic strategy. The development of long-circulating PEG and targeting liposomes is a major advance in drug delivery. However, the techniques used in liposome preparation mainly involve conventional liposomes, which have a short half-life, high concentrations in the liver and spleen reticuloendothelial system, and no active targeting.
Four kinds of paclitaxel liposomes were prepared and characterized by various analytical techniques. The long-term targeting effect of liposomes was verified by fluorescence detection methods in vivo and in vitro. Pharmacokinetic and acute toxicity tests were conducted in ICR mice to evaluate the safety of different paclitaxel preparations. The antitumor activity of ES-SSL-PTX was investigated in detail using in vitro and in vivo human breast cancer MCF-7 cell models.
ER-targeting liposomes had a particle size of 137.93±1.22 nm and an acceptable encapsulation efficiency of 88.07±1.25%. The liposome preparation is best stored at 4°C, and is stable for up to 48 hrs. Cytotoxicity test on MCF-7 cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. We used the near-infrared fluorescence imaging technique to confirm that ES-SSL-PTX was effectively targeted and could quickly and specifically identify the tumor site. Pharmacokinetics and acute toxicity in vivo experiments were carried out. The results showed that ES-SSL-PTX could significantly prolong the half-life of the drug, increase its circulation time in vivo, improve its bioavailability and reduce its toxicity and side effects. ES-SSL-PTX can significantly improve the pharmacokinetic properties of paclitaxel, avoid allergic reaction of the original solvent, increase antitumor efficacy and reduce drug toxicity and side effects.
ES-SSL-PTX has great potential for improving the treatment of breast cancer, thereby improving patient prognosis and quality of life.
乳腺癌是女性癌症死亡的主要原因。抑制癌细胞增殖的化疗被认为是最重要的治疗策略。长循环 PEG 和靶向脂质体的发展是药物输送的重大进展。然而，脂质体制备中使用的技术主要涉及传统脂质体，其半衰期短，肝和脾网状内皮系统浓度高，没有主动靶向性。
采用多种分析技术制备并表征了四种紫杉醇脂质体。通过体内和体外荧光检测方法验证了脂质体的长期靶向效果。在 ICR 小鼠中进行药代动力学和急性毒性试验，以评估不同紫杉醇制剂的安全性。使用体外和体内人乳腺癌 MCF-7 细胞模型详细研究了 ES-SSL-PTX 的抗肿瘤活性。
ER 靶向脂质体的粒径为 137.93±1.22nm，包封率为 88.07±1.25%。脂质体制剂最好在 4°C 下储存，最长稳定时间可达 48 小时。MCF-7 细胞的细胞毒性试验表明，与游离紫杉醇相比，脂质体具有更强的细胞毒性。我们使用近红外荧光成像技术证实 ES-SSL-PTX 能够有效靶向，并能够快速、特异性地识别肿瘤部位。进行了体内药代动力学和急性毒性实验。结果表明，ES-SSL-PTX 能显著延长药物的半衰期，增加其在体内的循环时间，提高其生物利用度，降低其毒性和副作用。ES-SSL-PTX 能显著改善紫杉醇的药代动力学特性，避免原溶剂的过敏反应，提高抗肿瘤疗效，降低药物毒性和副作用。
ES-SSL-PTX 具有改善乳腺癌治疗的巨大潜力，从而改善患者的预后和生活质量。
