Stella Barbara, Peira Elena, Dianzani Chiara, Gallarate Marina, Battaglia Luigi, Gigliotti Casimiro Luca, Boggio Elena, Dianzani Umberto, Dosio Franco
Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, Italy.
Dipartimento di Scienze della Salute, University of Eastern Piedmont Amedeo Avogadro, Via P.Solaroli, 15, 28100 Novara, Italy.
Nanomaterials (Basel). 2018 Feb 16;8(2):110. doi: 10.3390/nano8020110.
Solid lipid nanoparticles (SLNs) comprise a versatile drug delivery system that has been developed for the treatment of a variety of diseases. The present study will investigate the feasibility of entrapping an active doxorubicin prodrug (a squalenoyl-derivative) in SLNs. The doxorubicin derivative-loaded SLNs are spherically shaped, have a mean diameter of 300-400 nm and show 85% w/w drug entrapment efficiency. The effects on cell growth of loaded SLNs, free doxorubicin and the prodrug have been examined using cytotoxicity and colony-forming assays in both human ovarian cancer line A2780 wild-type and doxorubicin-resistant cells. Further assessments as to the treatment's ability to induce cell death by apoptosis have been carried out by analyzing annexin-V staining and the activation of caspase-3. The in vitro data demonstrate that the delivery of the squalenoyl-doxorubicin derivative by SLNs increases its cytotoxic activity, as well as its apoptosis effect. This effect was particularly evident in doxorubicin-resistant cells.
固体脂质纳米粒（SLNs）是一种多功能药物递送系统，已被开发用于治疗多种疾病。本研究将探讨在固体脂质纳米粒中包载活性阿霉素前药（一种角鲨烯酰衍生物）的可行性。载有阿霉素衍生物的固体脂质纳米粒呈球形，平均直径为300 - 400纳米，药物包封率为85%（重量/重量）。已使用细胞毒性和集落形成试验，在人卵巢癌细胞系A2780野生型和阿霉素耐药细胞中检测了载药固体脂质纳米粒、游离阿霉素和前药对细胞生长的影响。通过分析膜联蛋白V染色和半胱天冬酶-3的激活，进一步评估了该治疗诱导细胞凋亡的能力。体外数据表明，固体脂质纳米粒递送角鲨烯酰阿霉素衍生物可增强其细胞毒性活性及其凋亡效应。这种效应在阿霉素耐药细胞中尤为明显。
