Radu Ionut-Cristian, Hudita Ariana, Zaharia Catalin, Stanescu Paul O, Vasile Eugenia, Iovu Horia, Stan Miriana, Ginghina Octav, Galateanu Bianca, Costache Marieta, Langguth Peter, Tsatsakis Aristidis, Velonia Kelly, Negrei Carolina
Advanced Polymer Materials Group, University Politehnica of BucharestBucharest, Romania.
Department of Biochemistry and Molecular Biology, University of BucharestBucharest, Romania.
Front Pharmacol. 2017 Aug 2;8:508. doi: 10.3389/fphar.2017.00508. eCollection 2017.
The aim of this study was to address one of the major challenges of the actual era of nanomedicine namely, the bioavailability of poorly water soluble drugs such as Silymarin. We developed new, biodegradable, and biocompatible nanosized shuttles for Silymarin targeted delivery in colon-cancer cells. The design of these 100 nm sized carrier nanoparticles was based on natural polymers and their biological properties such as cellular uptake potential, cytotoxicity and 3D penetrability were tested using a colon cancer cell line (HT-29) as the culture model. Comparative scanning electron microscopy (SEM) and atomic force microscopy (AFM) measurements demonstrated that the Silymarin loaded Poly(3-HydroxyButyrate-co-3-HydroxyValerate) (PHBHV) nanocarriers significantly decreased HT-29 cells viability after 6 and 24 h of treatment. Moreover, like toxicity studies on multicellular tumor spheroids showed that the Silymarin loaded PHBHV nanocarriers are able to penetrate 3D micro tumors and significantly reduce their size.
本研究的目的是解决纳米医学当前时代的主要挑战之一,即水不溶性药物(如西利马林)的生物利用度问题。我们开发了新型、可生物降解且生物相容的纳米级载体,用于西利马林在结肠癌细胞中的靶向递送。这些尺寸为100纳米的载体纳米颗粒的设计基于天然聚合物,并以结肠癌细胞系(HT - 29)作为培养模型测试了它们的生物学特性,如细胞摄取潜力、细胞毒性和三维穿透性。比较扫描电子显微镜(SEM)和原子力显微镜(AFM)测量结果表明,负载西利马林的聚(3 - 羟基丁酸酯 - 共 - 3 - 羟基戊酸酯)(PHBHV)纳米载体在处理6小时和24小时后显著降低了HT - 29细胞的活力。此外,对多细胞肿瘤球体的毒性研究表明,负载西利马林的PHBHV纳米载体能够穿透三维微肿瘤并显著减小其尺寸。