Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
Department of Chemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada.
ACS Appl Mater Interfaces. 2024 Feb 28;16(8):9690-9701. doi: 10.1021/acsami.3c16330. Epub 2024 Feb 15.
The development of in vitro models recapitulating nanoparticle transport under physiological flow conditions is of great importance for predicting the efficacy of nanoparticle drug carriers. Liposomes are extensively used for drug delivery owing to their biocompatibility and biodegradability and the ability to carry both hydrophilic and hydrophobic compounds. Here, we used a library of liposomes with various dimensions and a microfluidic platform comprising a large array of uniformly sized breast cancer spheroids to explore size-dependent liposome internalization and retention in the spheroids under close-to-physiological interstitial conditions. Such a platform showed promising applications in the preclinical screening of small molecule drugs; however, the capability to deliver nanoparticles in the spheroid interior under close-to-physiological flow conditions was not explored. For the liposomes with diameters in the range of 45-200 nm, we show experimentally and by simulations that in comparison with liposome delivery solely by diffusion, flow significantly enhances liposome internalization in the microgels and mitigates the size-dependent spheroid penetration by the liposomes. The utility of the microfluidic platform was validated by evaluating the efficacy of clinically approved doxorubicin-loaded liposomes (Doxil), which exhibited superior retention in the spheroids under flow conditions, in comparison with free doxorubicin. This MF platform can serve as an in vitro model for screening the efficacy of drugs encapsulated in liposomes and find applications for screening other types of nanoparticle carriers for vaccine delivery, diagnostics, and skincare.
在生理流动条件下再现纳米颗粒传输的体外模型的发展对于预测纳米颗粒药物载体的功效非常重要。由于其生物相容性和可生物降解性以及携带亲水性和疏水性化合物的能力，脂质体被广泛用于药物输送。在这里，我们使用了一系列具有不同尺寸的脂质体和一个包含大量均匀尺寸乳腺癌球体的微流控平台，来探索在接近生理间质条件下，尺寸依赖性的脂质体在球体中的内化和保留。该平台在小分子药物的临床前筛选中显示出有希望的应用，但在接近生理流动条件下向球体内部输送纳米颗粒的能力尚未得到探索。对于直径在 45-200nm 范围内的脂质体，我们通过实验和模拟表明，与仅通过扩散的脂质体输送相比，流动显著增强了微凝胶中脂质体的内化，并减轻了脂质体对球体的尺寸依赖性穿透。该微流控平台的实用性通过评估临床批准的多柔比星负载脂质体（Doxil）的功效得到了验证，与游离多柔比星相比，Doxil 在流动条件下在球体中的保留效果更好。该 MF 平台可用作筛选包封在脂质体中的药物功效的体外模型，并可用于筛选用于疫苗输送、诊断和护肤的其他类型的纳米颗粒载体。
