Hydrophobic Effects in the Critical Destabilization and Release Dynamics of Degradable Multilayer Films
Hydrophobic Effects in the Critical Destabilization and Release Dynamics of Degradable Multilayer Films
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DOI：
10.1021/cm802972d
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发表时间：
2009-03-24
影响因子：
8.6
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Smith, Renee C.;Leung, Amy;Hammond, Paula T.
最近的研究已经强调了水解可降解的静电逐层膜作为能够多药剂释放的通用药物递送系统的能力。这些薄膜的一个关键要素是通过引发表面侵蚀机制来获得精确控制释放的潜力。在这里，我们试图确定在何种程度上操纵的化学结构可以用来控制释放从水解可降解的层层膜通过修改的可降解聚阳离子。为了实现这一目标，薄膜组成的聚（β-氨基酯），不同的二丙烯酸酯单体的选择，和模型生物药物，硫酸葡聚糖，被用来确定的作用，烷基链的长度，空间位阻，和疏水性的释放动力学。如使用辛醇：水系数所确定的，在临界聚阳离子疏水性之上，膜变得快速不稳定并快速释放其内容物。这些研究结果表明，在这些独特的静电组件，水解敏感性不仅取决于疏水性，但疏水组合物，电荷密度和静电离子对的稳定性之间的复杂平衡。计算确定辛醇：水系数允许可靠的预测释放动力学。辛醇：水系数和释放持续时间之间的相关性的确定将使先进的工程生产定制的药物递送系统。
Recent research has highlighted the ability of hydrolytically degradable electrostatic layer-by-layer films to act as versatile drug delivery systems capable of multiagent release. A key element of these films is the potential to gain precise control of release by evoking a surface-erosion mechanism. Here we sought to determine the extent to which manipulation of chemical structure could be used to control release from hydrolytically degradable layer-by-layer films through modification of the degradable polycation. Toward this goal, films composed of poly(beta-amino ester)s, varying only in the choice of diacrylate monomer, and the model biological drug, dextran sulfate, were used to ascertain the role of alkyl chain length, steric hindrance, and hydrophobicity on release dynamics. Above a critical polycation hydrophobicity, as determined using octanol:water coefficients, the film becomes rapidly destabilized and quickly released its contents. These findings indicate that in these unique electrostatic assemblies, hydrolytic susceptibility is dependent not only on hydrophobicity but a complex balance between hydrophobic composition, charge density, and stability of electrostatic ion pairs. Computational determination of octanol:water coefficients allowed for the reliable prediction of release dynamics. The determination of a correlation between the octanol:water coefficient and release duration will enable advanced engineering to produce custom drug delivery systems.