体内分布
纳米颗粒
药物输送
活体显微镜检查
外渗
动力学
纳米载体
纳米技术
生物物理学
材料科学
Zeta电位
毒品携带者
化学
体外
体内
医学
病理
生物化学
生物
物理
生物技术
量子力学
作者
Zhuoxuan Li,Tatyana Kovshova,Julia Malinovskaya,Marat P. Valikhov,Pavel Melnikov,Nadezhda Osipova,Olga Maksimenko,Namrata Dhakal,Anastasia Chernysheva,V. P. Chekhonin,Svetlana Gelperina,Matthias G. Wacker
出处
期刊:Small
[Wiley]
日期:2023-12-28
被引量:1
标识
DOI:10.1002/smll.202306726
摘要
Polylactide-co-glycolide (PLG) nanoparticles hold immense promise for cancer therapy due to their enhanced efficacy and biodegradable matrix structure. Understanding their interactions with blood cells and subsequent biodistribution kinetics is crucial for optimizing their therapeutic potential. In this study, three doxorubicin-loaded PLG nanoparticle systems are synthesized and characterized, analyzing their size, zeta potential, morphology, and in vitro release behavior. Employing intravital microscopy in 4T1-tumor-bearing mice, real-time blood and tumor distribution kinetics are investigated. A mechanistic pharmacokinetic model is used to analyze biodistribution kinetics. Additionally, flow cytometry is utilized to identify cells involved in nanoparticle hitchhiking. Following intravenous injection, PLG nanoparticles exhibit an initial burst release (<1 min) and rapidly adsorb to blood cells (<5 min), hindering extravasation. Agglomeration leads to the clearance of one carrier species within 3 min. In stable dispersions, drug release rather than extravasation remains the dominant pathway for drug elimination from circulation. This comprehensive investigation provides valuable insights into the interplay between competing kinetics that influence the lifecycle of PLG nanoparticles post-injection. The findings advance the understanding of nanoparticle behavior and lay the foundation for improved cancer therapy strategies using nanoparticle-based drug delivery systems.
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