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多层药物洗脱生物可吸收缝合线设计空间的理论研究

Theoretical Investigation of Design Space for Multi Layer Drug Eluting Bioresorbable Suture Threads.

作者信息

Casalini Tommaso, Rossi Filippo, Brizielli Luisa, Perale Giuseppe

机构信息

Institute of Mechanical Engineering and Material Engineering, Department of Innovative Technologies, SUPSI, 6928 Manno, Switzerland.

Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.

出版信息

Curr Pharm Biotechnol. 2019;20(4):332-345. doi: 10.2174/1389201020666190206200411.

Abstract

BACKGROUND

The work presented here is focused on the development of a comprehensive theoretical model for the description of drug release from a double - layer bioresorbable suture thread and the therapeutic efficacy of the active compounds delivered in the surrounding tissue.

METHODS

In particular, the system under investigation is composed of a core of slow-degrading polylactic- acid-co-ε-caprolactone (PLCL), where an antibiotic compound (Vancomycin) is loaded, surrounded by a shell of a fast-degrading polylactic-co-glycolic acid (PLGA) which contains an anesthetic drug (Lidocaine hydrochloride) for the post-surgical pain relief.

RESULTS

This system is of potential interest for the combined effects provided by the different active molecules, but the different release and polymer degradation dynamics, as well as their mutual influence, do not allow an intuitive a priori evaluation of device behavior, which can be rationalized through mathematical modeling. The model takes into account the main involved phenomena (polymer degradation and diffusion of the drugs within the device and the tissue, where they are metabolized) and their synergic effects on the overall system behavior.

CONCLUSION

Model results are discussed in order to quantify the impact of the main design parameters on device performances, thanks to the use of phase diagrams (which show drug effect in time and space) whose insights are summarized in order to determine a design space according to the specific needs.

摘要

背景

本文所呈现的工作聚焦于开发一个综合理论模型,用于描述双层生物可吸收缝合线的药物释放以及在周围组织中递送的活性化合物的治疗效果。

方法

具体而言,所研究的系统由一个缓慢降解的聚乳酸 - 共 - ε - 己内酯(PLCL)核心组成,其中负载了一种抗生素化合物(万古霉素),周围是一层快速降解的聚乳酸 - 乙醇酸共聚物(PLGA)外壳,该外壳含有用于术后止痛的麻醉药物(盐酸利多卡因)。

结果

该系统因不同活性分子提供的联合效应而具有潜在意义,但不同的释放和聚合物降解动力学以及它们之间的相互影响,使得无法对装置行为进行直观的先验评估,而这可以通过数学建模来合理化。该模型考虑了主要涉及的现象(聚合物降解以及药物在装置和组织内的扩散,药物在组织中会被代谢)以及它们对整个系统行为的协同效应。

结论

讨论了模型结果,以便通过使用相图(展示药物在时间和空间上的效应)来量化主要设计参数对装置性能的影响,总结相图的见解以根据特定需求确定设计空间。

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