负载阿霉素的磁性 PLGA 纳米颗粒在兔体内的同时治疗和诊断应用。
Simultaneous therapeutic and diagnostic applications of magnetic PLGA nanoparticles loaded with doxorubicin in rabbit.
发表日期:2024 Aug 31
作者:
Zahra Salmasi, Hossein Kamali, Hanieh Rezaee, Faezeh Nazeran, Zahra Jafari, Frarhad Eisvand, Manoocher Teymouri, Elnaz Khordad, Jafar Mosafer
来源:
Drug Delivery and Translational Research
摘要:
在本研究中,DOX(阿霉素)和 Fe3O4 磁性纳米晶体(SPION(超顺磁性氧化铁纳米晶体))被封装在 PLGA-PEG:聚(丙交酯-共-乙交酯)-b-聚(乙二醇)纳米颗粒中用于治疗诊断目的。最终制备的制剂被称为 NP(纳米粒子),其粒径平均直径约为 209 nm,饱和磁化强度值为 1.65 emu/g。与 pH 7.4 相比,NP 在 pH 5.5 下显示出更快的 DOX 释放。此外,与单独使用 Free-DOX 相比,NPs 在 C6 胶质瘤癌细胞中的细胞毒性作用有所增强。为了进行体内研究,2.2公斤重的兔子通过耳朵的中央关节前静脉注射纳米颗粒制剂。此外,通过 MR(磁共振)和荧光成像技术描绘了兔子器官的图像。与对照兔子相比,IV(静脉内)注射 NP 的兔子的 T2(松弛时间)加权 MR 图像中观察到负对比度(暗信号)。注射 NP 的兔子的器官荧光图像显示出高密度的红色,这与 DOX 在肝脏和肾脏器官中的积累有关。这些数据表明纳米颗粒对心脏没有细胞毒性作用。另外,不同器官的组织病理学检测结果表明,接受NPs和Free-DOX的组几乎相似,没有看到显着差异,但心脏组织中NPs的病理作用明显小于Free-DOX。 。此外,还对静脉注射 NP 和 Free-DOX 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 Free-DOX 相比,NPs 可以增强 DOX 在血清中的保留。总而言之,我们的目标是生产一种强大的递送纳米系统,以发挥其在双重治疗和诊断应用中的潜力,称为治疗诊断剂。© 2024。控释协会。
In this study, DOX (Doxorubicin) and Fe3O4 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 T2 (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.© 2024. Controlled Release Society.