Simultaneous therapeutic and diagnostic applications of magnetic PLGA nanoparticles loaded with doxorubicin in rabbit.

IF 5.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Drug Delivery and Translational Research Pub Date : 2025-02-01 Epub Date: 2024-08-31 DOI:10.1007/s13346-024-01693-9

Zahra Salmasi, Hossein Kamali, Hanieh Rezaee, Faezeh Nazeran, Zahra Jafari, Frarhad Eisvand, Manouchehr Teymouri, Elnaz Khordad, Jafar Mosafer

{"title":"Simultaneous therapeutic and diagnostic applications of magnetic PLGA nanoparticles loaded with doxorubicin in rabbit.","authors":"Zahra Salmasi, Hossein Kamali, Hanieh Rezaee, Faezeh Nazeran, Zahra Jafari, Frarhad Eisvand, Manouchehr Teymouri, Elnaz Khordad, Jafar Mosafer","doi":"10.1007/s13346-024-01693-9","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"770-785"},"PeriodicalIF":5.7000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Delivery and Translational Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13346-024-01693-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/31 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

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.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

载入多柔比星的磁性聚乳酸（PLGA）纳米粒子在兔子身上的同步治疗和诊断应用。

本研究将 DOX（多柔比星）和 Fe3O4 磁性纳米晶体（SPIONs，超顺磁性氧化铁纳米晶体）封装在 PLGA-PEG：聚乳酸-聚乙二醇纳米颗粒中，用于治疗目的。最终制备的制剂被称为 NPs（纳米颗粒），其平均直径为 209 纳米，饱和磁化值为 1.65 emu/g。与 pH 值 7.4 相比，NPs 在 pH 值 5.5 时释放 DOX 的速度更快。此外，与单用游离 DOX 相比，NPs 对 C6 胶质瘤癌细胞的细胞毒性也有所增加。在体内研究中，2.2 千克重的兔子通过耳部中央关节前静脉注射了 NPs 制剂。此外，还通过磁共振和荧光成像技术描绘了兔子器官的图像。与对照组相比，静脉注射 NPs 的兔子的 T2（弛豫时间）加权磁共振图像出现了负对比（暗信号）。注射了 NPs 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蓄积有关。这些数据表明，NPs 对心脏没有细胞毒性作用。此外，不同器官的组织病理学检测结果表明，接受 NPs 和 Free-DOX 治疗的各组几乎相似，除心脏组织的病理效应明显低于 Free-DOX 外，其他器官无明显差异。此外，还对静脉注射 NPs 和 Free-DOX 的兔子的血清和全血进行了药代动力学研究。药代动力学参数显示，与 Free-DOX 相比，NPs 可提高 DOX 在血清中的保留率。总之，我们的目标是制备出一种强大的给药纳米系统，使其具有治疗和诊断双重应用的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY

CiteScore

11.70

自引率

1.90%

发文量

160

期刊介绍： The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.