The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, PR China.
The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, PR China.
Eur J Pharm Sci. 2019 Dec 1;140:105070. doi: 10.1016/j.ejps.2019.105070. Epub 2019 Sep 10.
Homogeneous PEGylated lipid bilayer coated highly ordered MSNs (PLMSNs) which were systematically optimized and characterized to co-encapsulate paclitaxel (Tax) and curcumin (Cur) were verified to manifest prolonged and enhanced cytotoxic effect against canine breast cancer cells in our previous study. In this article, we took further study of the pharmacokinetic property, cellular uptake, subcellular localization, in vivo distribution and tumor accumulation ability, and treatment efficacy of the drug delivery system. The results revealed that the delivery system could significantly increase the AUC of two drugs, and the anti-tumor effect showed that both intravenous and intratumoral administration group better controlled the tumor weight than that of other groups (P < .05), and the anti-tumor rates were 58.4% and 58.3% respectively. Cell uptake and localization study showed that PLMSNs could effectively carry drugs into cancer cells with sustained release characteristics. The subcellular localization of PLMSNs was mainly in lysosomes and mitochondria. In vivo fluorescence tracing results showed that PLMSNs could be effectively accumulated in the tumor site. The results revealed that the delivery system could effectively reduce the clinical dosage of drugs and reduce its toxic side effects, effectively carry drugs into cancer cells, and exhibit good targeting characteristics for breast cancer.
在之前的研究中，我们验证了经过系统优化和特性分析的均一化聚乙二醇化脂质双层包被的高度有序介孔硅纳米粒（PLMSNs）能够共包封紫杉醇（Tax）和姜黄素（Cur），从而表现出延长和增强的抗犬乳腺癌细胞毒性作用。在本文中，我们进一步研究了该给药系统的药代动力学特性、细胞摄取、亚细胞定位、体内分布和肿瘤积累能力以及治疗效果。结果表明，该给药系统能够显著增加两种药物的 AUC，且抗肿瘤效果表明，与其他组相比，静脉内和瘤内给药组能够更好地控制肿瘤重量（P < .05），抗肿瘤率分别为 58.4%和 58.3%。细胞摄取和定位研究表明，PLMSNs 能够有效地携带药物进入具有持续释放特性的癌细胞。PLMSNs 的亚细胞定位主要在溶酶体和线粒体中。体内荧光示踪结果表明，PLMSNs 能够有效地在肿瘤部位积累。结果表明，该给药系统能够有效降低药物的临床剂量，减少其毒副作用，有效地将药物递送到癌细胞中，并表现出针对乳腺癌的良好靶向特性。
