Affiliation:
1. Department of Pharmacy National University of Singapore 4 Science Drive 2 Singapore 117544 Singapore
2. D. Mendeleev University of Chemical Technology of Russia Miusskaya pl. 9 Moscow 125047 Russia
3. Department of Neurobiology V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology of the Ministry of Health of the Russian Federation Kropotkinskiy per. 23 Moscow 119034 Russia
Abstract
AbstractPolylactide‐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.
Funder
Ministry of Science and Higher Education of the Russian Federation
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry
Cited by
3 articles.
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