National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi\'an, China.
Department of Pharmacy, The First Affiliated Hospital of Xi\'an Jiaotong University, Xi\'an, China.
Curr Pharm Biotechnol. 2022;23(7):978-987. doi: 10.2174/1389201022666210604153738.
Due to the short biological half-life and serious side effects (especially for heart and kidney), the application of Doxorubicin (Dox) in clinical therapy is strictly limited. To overcome these shortcomings, a novel sustained release formulation of doxorubicin-loaded dextran-coated superparamagnetic iron oxide nanoparticles (Dox-DSPIONs) was prepared.
The purpose of this study was to evaluate the intracellular uptake behavior of Dox-DSPIONs and to investigate their pharmacokinetics and biodistribution properties.
Confocal laser scanning microscopy was employed to study the intracellular uptake and release properties of Dox from Dox-DSPIONs in SMMC-7721 cells. Simple high-performance liquid chromatography with fluorescence detection (HPLC-FLD) method was established to study the pharmacokinetics and biodistribution properties of Dox-DSPIONs in vivo after intravenous administration and compared with free Dox.
Intracellular uptake experiment indicated that Dox could be released sustainedly from Dox-DSPIONs over time. The pharmacokinetics parameters displayed that the T1/2and AUC of Dox-DSPIONs were higher than those of free Dox, while the C of Dox-DSPIONs was significantly lower than that of free drug. The biodistribution behaviors of the drug were altered by Dox-DSPIONs in mice, which showed obvious liver targeting, and significantly reduced the distribution of the drug in the heart and kidney.
Dox-DSPIONs have the sustained-release property in vitro and in vivo, which could significantly prolong blood circulation time, improve bioavailability, and reduce the side effects of Dox. Therefore, the novel formulation of the Dox-DSPIONs has the potential as a promising drug delivery system in cancer therapy.
由于阿霉素（Dox）的生物半衰期短且副作用严重（尤其是对心脏和肾脏），其在临床治疗中的应用受到严格限制。为了克服这些缺点，制备了载阿霉素的葡聚糖包覆超顺磁性氧化铁纳米粒子（Dox-DSPIONs）的新型缓释制剂。
本研究旨在评估 Dox-DSPIONs 的细胞内摄取行为，并研究其药代动力学和生物分布特性。
采用共聚焦激光扫描显微镜研究 Dox-DSPIONs 在 SMMC-7721 细胞中的细胞内摄取和释放特性。建立简单的高效液相色谱-荧光检测（HPLC-FLD）方法，研究 Dox-DSPIONs 静脉给药后的体内药代动力学和生物分布特性，并与游离 Dox 进行比较。
细胞内摄取实验表明，Dox 可从 Dox-DSPIONs 中持续释放。药代动力学参数显示，Dox-DSPIONs 的 T1/2和 AUC 高于游离 Dox，而 Dox-DSPIONs 的 C 明显低于游离药物。Dox-DSPIONs 在小鼠体内改变了药物的分布行为，表现出明显的肝脏靶向性，并显著减少了药物在心脏和肾脏中的分布。
Dox-DSPIONs 具有体外和体内的缓释特性，可显著延长血液循环时间，提高生物利用度，降低 Dox 的副作用。因此，Dox-DSPIONs 的新型制剂具有作为癌症治疗中一种有前途的药物传递系统的潜力。
