Layer-by-layer platform technology for small-molecule delivery.
Layer-by-layer platform technology for small-molecule delivery.
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DOI：
10.1002/anie.200902782
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发表时间：
2009
影响因子：
16.6
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Smith, Renee C.;Riollano, Mariawy;Leung, Amy;Hammond, Paula T.
小分子对生物功能的各个方面都至关重要，并且包括迄今为止上市的大多数药物。[1]然而，大量的小有机分子表现出低的水溶性，并且在开发中的所有药物失败中，> 40%是由于药物递送不足。随着高通量方法继续产生能够修正复杂疾病途径的无数化学实体，寻找以适当方式递送这些分子的有效和高效方法的压力增加。存在对递送具有精确时空控制的中性和疏水性小分子的不同集合的深刻需求。在这里，我们报道了一种新型的可固化膜系统，其能够从几乎任何表面递送小分子治疗剂，而不管几何形状或表面化学，具有通过水解自上而下降解的可编程零级释放动力学。虽然存在用于局部小分子递送的构建涂层的方法，但大多数依赖于基于扩散的释放，并且遭受推注倾倒、短释放时间尺度、苛刻的组装条件，复杂的制造和/或有限的治疗范围和结合。这些不利的特性极大地阻碍了它们的实用性。逐层（LbL）组装是一种基于互补化学相互作用的定向组装技术，其独特之处在于其能够在室温下通过简单、温和的水性制造条件以相关剂量产生具有广泛治疗剂的纳米级保形膜。然而，LbL一直无法满足对具有高度受控释放动力学的小分子递送的需求，并且尝试一直受到扩散受控速率、短释放时间尺度和通常不明确的释放机制的困扰。分子的直接吸收和载体如树枝状聚合物、胶束、纳米颗粒、单体环糊精和前药的使用已经不能克服这些障碍。[2-4]扩散动力学阻止了释放动力学的简易高级工程，并且释放常常通过增加系统复杂性来调制。对于许多药物，突释带来了增加的毒性风险，并且短时间尺度限制了一般适用性。
Small molecules are critical to every aspect of biological function, and comprise most medicines marketed to date.[1] Yet a large number of small organic molecules exhibit low aqueous solubility and> 40% of all drug failures in development are due to inadequate drug delivery. As high-throughput methods continue to produce a myriad of chemical entities able to amend complex disease pathways, there is increased pressure to find effective and efficient ways to deliver these molecules in an appropriate manner. There exists a profound need to deliver a diverse set of neutral and hydrophobic small molecules with exact spatiotemporal control. Here we report a novel ultrathin film system able to deliver small molecule therapeutics from virtually any surface, regardless of geometry or surface chemistry, with programmable zero order release kinetics through hydrolytic top down degradation.While methods to construct coatings for localized small molecule delivery exist, most rely on diffusion based release and suffer from bolus dumping, short release timescales, harsh assembly conditions, complex manufacturing and/or limited therapeutic scope and incorporation. These adverse characteristics have greatly hindered their utility. Layer-by-Layer (LbL) assembly, a directed assembly technique based on complementary chemical interactions, stands alone in its ability to create nanoscale, conformal films with a broad range of therapeutics at relevant doses via simple, mild aqueous manufacturing conditions at room temperature. Yet, LbL has been unable to address the demand for small molecule delivery with highly controlled release kinetics, and attempts have been plagued by diffusion-controlled rates, short release timescales, and often ill-defined release mechanisms. Direct absorption of molecules and use of carriers such as dendrimers, micelles, nanoparticles, monomeric cyclodextrins, and prodrugs have been unable to overcome these barriers.[2–4] Diffusion kinetics prevent facile advanced engineering of release dynamics, and release is often modulated by increasing system complexity. For many drugs, burst release carries an increased risk of toxicity and short timescales limit general applicability.
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DOI：
10.1073/pnas.0602884103
发表时间：
2006-07-05
影响因子：
11.1
作者：
Wood, Kris C.;Chuang, Helen F.;Hammond, Paula T.
通讯作者：
Hammond, Paula T.
影响因子：
8.6
作者：
Nguyen, Phuong M.;Zacharia, Nicole S.;Hammond, Paula T.
通讯作者：
Hammond, Paula T.
影响因子：
8.6
作者：
Smith, Renee C.;Leung, Amy;Hammond, Paula T.
通讯作者：
Hammond, Paula T.
影响因子：
10.8
作者：
Khopade, AJ;Caruso, F
通讯作者：
Caruso, F