Purpose

Due to low therapeutic efficacy and severe adverse reaction of systemic administration for coronary heart disease (CHD) therapy, we designed a novel local target delivery system, called Active hydraulic ventricular Support Drug delivery system (ASD). This study aims to investigate the potential advantages of ASD compared to intrapericardial (IPC) injection and factors affecting drug absorption through epicardium.

Methods

Liposoluble, water soluble and viscous solutions of cyanine 5 (Cy5) fluorescent dye were delivered individually through ASD and IPC in Sprague-Dawley (SD) rats and then tissues were isolated and observed by in vivo imaging system. Atria and ventricles of the heart were taken for the paraffin section and observed under a fluorescence microscope.

Results

The fluorescence intensity of Cy5 injected by ASD distributed in the heart was significantly higher than IPC injection. Whereas, the fluorescence signal spread in other tissues such as lung, liver, spleen, and kidney of ASD groups was much weaker. Moreover, when choosing liposoluble and viscous Cy5, the intensity of the heart turned stronger and fluorescence dye distributed in other tissues was lesser.

Conclusions

The application of ASD device may provide a promising route of drug delivery for CHD. Furthermore, increasing viscosity of the solution and liposolublity of the drug was beneficial to facilitate drug absorption through the epicardium.

中文翻译：

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ASD装置的药代动力学优势可促进药物通过心外膜吸收。

目的

由于冠心病（CHD）治疗的全身治疗的低疗效和严重不良反应，我们设计了一种新型的局部目标递送系统，称为主动液压心室支持药物递送系统（ASD）。这项研究旨在调查与心包内（IPC）注射相比，ASD的潜在优势以及影响通过心外膜吸收药物的因素。

方法

通过ASD和IPC将花青5（Cy5）荧光染料的脂溶性，水溶性和粘性溶液分别通过ASD和IPC递送到Sprague-Dawley（SD）大鼠中，然后分离组织并通过体内成像系统进行观察。取心房和心室作石蜡切片，并在荧光显微镜下观察。

结果

ASD注射到心脏的Cy5荧光强度明显高于IPC注射。然而，荧光信号在ASD组的其他组织（如肺，肝，脾和肾）中传播较弱。此外，在选择脂溶性和粘性的Cy5时，心脏的强度更强的导通和分布在其他组织中的荧光染料是较小的。

结论

ASD装置的应用可能为冠心病提供一种有希望的给药途径。此外，增加溶液的粘度和药物的脂溶性有利于促进药物通过心外膜的吸收。