MAD (multiagent delivery) nanolayer: delivering multiple therapeutics from hierarchically assembled surface coatings.

MAD (multiagent delivery) nanolayer: delivering multiple therapeutics from hierarchically assembled surface coatings.
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MAD(多药剂输送)纳米层:通过分层组装的表面涂层输送多种治疗药物。

DOI:
10.1021/la9017618
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发表时间:
2009-12-15
期刊:
Langmuir : the ACS journal of surfaces and colloids
影响因子:
--
通讯作者:
Hammond PT
Hammond PT
中科院分区:
其他
文献类型:
--
作者:
Kim BS;Smith RC;Poon Z;Hammond PT

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我们提出了一种可水解降解的聚合物多层膜,它可以从表面共同递送具有不同化学特性(带电生物大分子和中性疏水小分子)的多种治疗药物。这种多剂递送(MAD)纳米层系统集成了可水解降解的聚(β-氨基酯)作为结构成分,以控制多层膜的降解以释放活性治疗大分子,以及嵌入在两亲嵌段共聚物胶束载体中的疏水药物,否则很难包括在多层膜中。通过改变多层中的阴离子治疗剂(肝素和硫酸葡聚糖),我们研究了如何使用不同的结构成分来控制MAD纳米层中多种治疗剂的释放动力学。并对其体外抑制平滑肌细胞生长的效果进行了评价。一种带电荷的大分子肝素和一种小的疏水性药物紫杉醇的双重递送被发现是协同的,有利于有效的治疗活性。此外,我们还比较了经典的浸渍法和自动喷雾lbl技术。Spray-LbL显著缩短了薄膜处理时间,同时保留了MAD纳米层的特征释放曲线。由于LbL组装的高度通用性和可调节性,我们预计MAD纳米层可以提供一个独特的平台,用于从大分子到小分子的多种治疗,并具有不同的释放谱,用于生物和生物医学表面涂层。
We present the hydrolytically degradable polymeric multilayer films that can co-deliver multiple therapeutics of differing chemical characteristics (charged biomacromolecules and neutral hydrophobic small molecules) from a surface. This multi-agent-delivery (MAD) nanolayer system integrates the hydrolytically degradable poly(β-amino ester) as a structural component to control the degradation of the multilayers to release active therapeutic macromolecules, as well as hydrophobic drugs imbedded within amphiphilic block copolymer micellar carriers within layer-by-layer (LbL) films, which would otherwise be difficult to include within the multilayers. By varying the anionic therapeutic agents (heparin and dextran sulfate) within the multilayer, we examine how different structural components can be used to control the release kinetics of multiple therapeutics from MAD nanolayers. Controlled release profiles and the in vitro efficacy of the MAD nanolayers in suppressing the growth of human smooth muscle cell lines were evaluated. The dual delivery of a charged macromolecular heparin and a small hydrophobic drug, paclitaxel, is found to be synergistic and beneficial toward effective therapeutic activity. Furthermore, we compared the classical dipping method we employed here with an automated spray-LbL technique. Spray-LbL significantly facilitates film processing time while preserving the characteristic release profiles of the MAD nanolayers. With the highly versatile and tunable nature of LbL assembly, we anticipate that MAD nanolayers can provide a unique platform for delivering multiple therapeutics from macromolecular to small molecules with distinct release profiles for applications in biological and biomedical surface coatings.
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