Salmasi Zahra, Kamali Hossein, Rezaee Hanieh, Nazeran Faezeh, Jafari Zahra, Eisvand Frarhad, Teymouri Manouchehr, Khordad Elnaz, Mosafer Jafar
Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Drug Deliv Transl Res. 2025 Feb;15(2):770-785. doi: 10.1007/s13346-024-01693-9. Epub 2024 Aug 31.
In this study, DOX (Doxorubicin) and FeO magnetic nanocrystals (SPIONs (Superparamagnetic iron oxide nanocrystals)) were encapsulated in the PLGA-PEG: poly(lactide-co-glycolide)-b-poly(ethylene glycol) nanoparticles for theranostic purposes. The final prepared formulation which is called NPs (Nanoparticles) exhibited a particle size with a mean diameter of ~ 209 nm and a sufficient saturation magnetization value of 1.65 emu/g. The NPs showed faster DOX release at pH 5.5 compared to pH 7.4. Also, the cytotoxicity effect of NPs increased compared to Free-DOX alone in C6 glioma cancer cells. For in vivo investigations, the 2.2 Kg rabbits were injected with NPs formulations via a central articular anterior vein in their ears. Furthermore, the images of rabbit organs were depicted via MR (Magnetic resonance) and fluorescent imaging techniques. A negative contrast (dark signal) was observed in T (Relaxation Time) weighted MR images of IV (Intravenously)-injected rabbits with NPs compared to the control ones. The organ's florescent images of NPs-injected rabbits showed a high density of red color related to the accumulation of DOX in liver and kidney organs. These data showed that the NPs have no cytotoxicity effect on the heart. Also, the results of histopathological tests of different organs showed that the groups receiving NPs and Free-DOX were almost similar and no significant difference was seen, except for the cardiac tissue in which the pathological effects of NPs were significantly less than the Free-DOX. Additionally, pharmacokinetic studies were also conducted at the sera and whole bloods of IV-injected rabbits with NPs and Free-DOX. The pharmacokinetic parameters showed that NPs could enhance the DOX retention in the serum compared to the Free-DOX. Altogether, we aimed to produce a powerful delivery nanosystem for its potential in dual therapeutic and diagnostic applications which are called theranostic agents.
在本研究中，为了实现诊疗一体化目的，将阿霉素（DOX）和氧化亚铁磁性纳米晶体（超顺磁性氧化铁纳米晶体，SPIONs）封装于聚乳酸-羟基乙酸共聚物-聚乙二醇（PLGA-PEG：聚（丙交酯-共-乙交酯）-b-聚（乙二醇））纳米颗粒中。最终制备的制剂称为纳米颗粒（NPs），其粒径平均直径约为209 nm，饱和磁化强度值充足，为1.65 emu/g。与pH 7.4相比，纳米颗粒在pH 5.5时阿霉素释放更快。此外，与单独使用游离阿霉素相比，纳米颗粒在C6胶质瘤癌细胞中的细胞毒性作用增强。对于体内研究，给2.2千克重的兔子通过其耳部的中央关节前静脉注射纳米颗粒制剂。此外，通过磁共振（MR）和荧光成像技术描绘兔子器官的图像。与对照组相比，静脉注射纳米颗粒的兔子的T（弛豫时间）加权MR图像中观察到负性对比（暗信号）。注射纳米颗粒的兔子的器官荧光图像显示，与阿霉素在肝脏和肾脏器官中的积累相关的红色高密度。这些数据表明纳米颗粒对心脏没有细胞毒性作用。此外，不同器官的组织病理学测试结果表明，接受纳米颗粒和游离阿霉素的组几乎相似，未见显著差异，但心脏组织除外，其中纳米颗粒的病理作用明显小于游离阿霉素。此外，还对静脉注射纳米颗粒和游离阿霉素的兔子的血清和全血进行了药代动力学研究。药代动力学参数表明，与游离阿霉素相比，纳米颗粒可提高阿霉素在血清中的保留率。总之，我们旨在制备一种强大的递送纳米系统，因其在双重治疗和诊断应用中的潜力，即所谓的诊疗试剂。
