The architecture and biological performance of drug-loaded LbL nanoparticles.
The architecture and biological performance of drug-loaded LbL nanoparticles.
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DOI：
10.1016/j.biomaterials.2013.03.059
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发表时间：
2013-07
期刊：
影响因子：
14
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Morton, Stephen W.;Poon, Zhiyong;Hammond, Paula T.
逐层（Layer-by-Layer，LbL）纳米颗粒是一类新兴的治疗载体，其提供对关键设计参数的精确控制，从而促进改善药物和载体药代动力学，并增强分子靶向能力。本文通过将这些系统建立为药物载体来推进这些系统的发展，其手段是控制药物在全身环境中的释放，并延缓颗粒从循环中的清除，促进含药系统的生物分布的改善。使用双荧光跟踪在体内，这项工作建立了一个强大的手段筛选库的LBL系统产生的，提供同时分辨率超过持久性和生物分布的药物和载体后，全身给药的单颗粒制剂。采用PLGA含药物的核心作为LbL沉积的基底，制造了一系列包衣系统，以研究这些膜稳定药物递送以及改善药物和载体的药代动力学的能力。在体循环的前30分钟内，观察到分层结构的不同制剂的肝脏蓄积显著减少。LbL结构使替代药物cardiogreen的肝脏定位相对于天然PLGA纳米颗粒减少10- 25%ID/g，并调节肝脏中的载体积累> 50%ID/g。此外，在包衣系统中观察到药物的持久性增强，药物半衰期从游离药物的2-3分钟和未包衣核心的1.87小时显著增加至包衣系统的4.17小时和4.54小时。这些系统提供了一个令人兴奋的模块化平台，可以改善治疗剂的药代动力学特性，减少药物从纳米颗粒中的推注释放，并提高药物在体内的安全性和循环半衰期，证明它们具有高度的临床相关性，并且是未来开发分子靶向和组合治疗剂的有前途的方法。
Layer-by-Layer (LbL) nanoparticles are an emerging class of therapeutic carriers that afford precise control over key design parameters that facilitate improved drug and carrier pharmacokinetics, and enhanced molecular-targeting capabilities. This paper advances the development of these systems by establishing them as drug carriers, with the means to control drug release in a systemic environment and retard particle clearance from circulation, promoting improved biodistribution of the drug-containing system. Using dual-fluorescent tracking in vivo, this work establishes a robust means of screening libraries of LbL systems generated, affording simultaneous resolution over persistence and biodistribution of both the drug and carrier following systemic administration of a single particle formulation. Employing a PLGA drug-containing core as a substrate for LbL deposition, a range of coated systems were fabricated to investigate the abilities of these films to stabilize drug for delivery as well as to improve the pharmacokinetics of both the drug and carrier. Significant reductions in liver accumulation were observed for different formulations of the layered architectures within the first 30 minutes of systemic circulation. LbL architectures diminished liver localization of the surrogate drug, cardiogreen, by 10–25% ID/g relative to native PLGA nanoparticles and modulated carrier accumulation in the liver >50% ID/g. Further, enhanced persistence of the drug was observed with the coated systems, significantly increasing the drug half-life from 2–3 minutes for free drug and 1.87h for the uncoated core to 4.17h and 4.54h for the coated systems. These systems provide an exciting, modular platform that improves the pharmacokinetic properties of the therapeutic, reduces bolus release of drug from nanoparticles, and enhances the safety and circulation half-life of the drug in vivo, proving them to be highly clinically-relevant and a promising approach for future development of molecularly-targeted and combination therapeutics.
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影响因子：
13.6
作者：
Chen ZG
通讯作者：
Chen ZG
影响因子：
5.8
作者：
Avgoustakis, K;Beletsi, A;Ithakissios, DS
通讯作者：
Ithakissios, DS
影响因子：
5.6
作者：
CULTY, M;SHIZARI, M;UNDERHILL, CB
通讯作者：
UNDERHILL, CB
影响因子：
15
作者：
Joester, D;Klein, E;Addadi, L
通讯作者：
Addadi, L
DOI：
10.1016/s0927-7757(00)00825-6
发表时间：
2001-06-30
影响因子：
5.2
作者：
Kwon, HY;Lee, JY;Kim, JH
通讯作者：
Kim, JH