Controlling in vivo stability and biodistribution in electrostatically assembled nanoparticles for systemic delivery.
Controlling in vivo stability and biodistribution in electrostatically assembled nanoparticles for systemic delivery.
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DOI：
10.1021/nl200636r
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发表时间：
2011-05-11
期刊：
影响因子：
10.8
通讯作者：
Hammond PT
中科院分区：
文献类型：
--
作者：
Poon Z;Lee JB;Morton SW;Hammond PT
本文演示了用于癌症应用的可系统递送的一层一层（LbL）纳米颗粒的生成。基于lbl的纳米颗粒被设计用于在体内导航并以可编程的方式提供治疗，是一种很有前途的替代药物递送系统；但由于缺乏构建LbL纳米膜的知识来模拟传统的纳米颗粒设计，以优化其在体内的系统递送，因此很少有证据表明它们在体内的系统递送。这些纳米载体在体内成功应用的关键是需要系统地分析膜结构和吸附的聚电解质外层对其药代动力学的影响，到目前为止还没有对这种纳米颗粒递送的新方法进行研究。在此，我们已经在稳定和控制多层纳米颗粒的系统分布方面迈出了第一步。我们的研究结果突出了LbL系统的独特特征：静电组装的纳米颗粒在体内的稳定性随着沉积层的增加而增加，最后一层吸附产生了一个关键的表面级联，这决定了纳米颗粒的表面化学和生物学特性。这种外聚电解质层不仅显著影响非特异性颗粒的摄取程度，而且影响纳米颗粒的生物分布。对于透明质酸（HA）外层，观察到较长的血液消除半衰期（~9 h）和低积聚（~ 10 - 15%荧光/g），说明这些系统可以设计为非常适合临床翻译。
This paper demonstrates the generation of systemically deliverable layer-by-layer (LbL) nanoparticles for cancer applications. LbL-based nanoparticles designed to navigate the body and deliver therapeutics in a programmable fashion are promising new and alternative systems for drug delivery; but there have been very few demonstrations of their systemic delivery in vivo due to a lack of knowledge in building LbL nanofilms that mimic traditional nanoparticle design to optimize delivery. The key to the successful application of these nanocarriers in vivo requires a systematic analysis of the influence of film architecture and adsorbed polyelectrolyte outer layer on their pharmacokinetics, which has thus far not been examined for this new approach to nanoparticle delivery. Herein, we have taken the first steps in stabilizing and controlling the systemic distribution of multilayer nanoparticles. Our findings highlight the unique character of LbL systems: the electrostatically assembled nanoparticles gain increased stability in vivo with larger numbers of deposited layers, and the final layer adsorbed generates a critical surface cascade, which dictates the surface chemistry and biological properties of the nanoparticle. This outer polyelectrolyte layer dramatically affects not only the degree of nonspecific particle uptake, but also the nanoparticle biodistribution. For hyaluronic acid (HA) outer layers, a long blood elimination half-life (~9 h) and low accumulation (~ 10–15 % recovered fluorescence/g) in the liver were observed, illustrating that these systems can be designed to be highly appropriate for clinical translation.
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