Modeling the Drug delivery Lifecycle of PLG Nanoparticles Using Intravital Microscopyстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 15 февраля 2024 г.
Аннотация:Polylactide-co-glycolide (PLG) nanoparticles hold immense promise for cancertherapy due to their enhanced efficacy and biodegradable matrix structure.Understanding their interactions with blood cells and subsequentbiodistribution kinetics is crucial for optimizing their therapeutic potential. Inthis study, three doxorubicin-loaded PLG nanoparticle systems aresynthesized and characterized, analyzing their size, zeta potential,morphology, and in vitro release behavior. Employing intravital microscopy in4T1-tumor-bearing mice, real-time blood and tumor distribution kinetics areinvestigated. A mechanistic pharmacokinetic model is used to analyzebiodistribution kinetics. Additionally, flow cytometry is utilized to identify cellsinvolved in nanoparticle hitchhiking. Following intravenous injection, PLGnanoparticles exhibit an initial burst release (<1 min) and rapidly adsorb toblood cells (<5 min), hindering extravasation. Agglomeration leads to theclearance of one carrier species within 3 min. In stable dispersions, drugrelease rather than extravasation remains the dominant pathway for drugelimination from circulation. This comprehensive investigation providesvaluable insights into the interplay between competing kinetics that influencethe lifecycle of PLG nanoparticles post-injection. The findings advance theunderstanding of nanoparticle behavior and lay the foundation for improvedcancer therapy strategies using nanoparticle-based drug delivery systems