Dandamudi Suman, Campbell Robert B
Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, 360 Huntington Avenue, 110 Mugar Hall, Boston, MA 02115, USA.
Biomaterials. 2007 Nov;28(31):4673-83. doi: 10.1016/j.biomaterials.2007.07.024. Epub 2007 Aug 3.
Chemotherapy is a popular treatment approach against cancer but significant uptake of drugs by normal tissues is still a major limitation. Magnetic drug targeting (MDT) has been used to improve localized drug delivery to interstitial tumor targets. MDT is now being developed to improve drug delivery to tumor vessels. We thus seek to understand the role of magnetite (MAG-C) in drug loading, influence on cytotoxicity and vascular targeting characteristics. The inclusion of MAG-C at lower concentrations (0.5 mg/ml) in cationic liposomes did not alter the efficiency of loading etoposide, but at higher concentrations (2.5 mg/ml) incorporation decreased from 80+/-3.4% to 44+/-4.26%. MAG-C reduced the incorporation of dacarbazine. The incorporation was significantly lower compared to liposomal etoposide, both in the presence and absence of MAG-C. The incorporation efficiency of vinblastine sulfate in cationic liposomes was similar for low and relatively high MAG-C content; values for incorporation were 21+/-0.11 and 23+/-2, respectively. Polyethylene-glycol improved the efficiency of loading chemotherapeutic agents regardless of drug type. Additionally, cytotoxicity and tumor vascular targeting characteristics of liposome therapeutics were not influenced by MAG-C. The components used to prepare magnetic liposomes for MDT should be optimized for maximum therapeutic benefit.
化疗是一种常用的抗癌治疗方法,但正常组织对药物的大量摄取仍是一个主要限制。磁性药物靶向(MDT)已被用于改善向间质肿瘤靶点的局部药物递送。目前正在开发MDT以改善向肿瘤血管的药物递送。因此,我们试图了解磁铁矿(MAG-C)在药物负载中的作用、对细胞毒性的影响以及血管靶向特性。在阳离子脂质体中加入较低浓度(0.5mg/ml)的MAG-C不会改变依托泊苷的负载效率,但在较高浓度(2.5mg/ml)时,包封率从80±3.4%降至44±4.26%。MAG-C降低了达卡巴嗪的包封率。无论有无MAG-C,其包封率均显著低于脂质体依托泊苷。低MAG-C含量和相对高MAG-C含量的阳离子脂质体中硫酸长春碱的包封效率相似;包封率分别为21±0.11和23±2。聚乙二醇提高了化疗药物的负载效率,与药物类型无关。此外,脂质体治疗剂的细胞毒性和肿瘤血管靶向特性不受MAG-C影响。用于制备MDT磁性脂质体的成分应进行优化,以获得最大治疗效益。