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聚合物基质中药物释放的多尺度机制:通过非线性理论模型进行验证

A multiscale mechanism of drug release from polymeric matrices: confirmation through a nonlinear theoretical model.

作者信息

Bacaita E S, Agop M

机构信息

Department of Physics, "Gheorghe Asachi" Technical University of Iasi, Prof. Dr Docent Dimitrie Mangeron Rd, No. 73, Iasi 700050, Romania.

出版信息

Phys Chem Chem Phys. 2016 Aug 21;18(31):21809-16. doi: 10.1039/c6cp02259f. Epub 2016 Jul 20.

DOI:10.1039/c6cp02259f
PMID:27436760
Abstract

In this paper, we propose a new approach for the dynamics of drug delivery systems, assimilated to complex systems, an approach based on concepts like fractality, non-differentiability, and multiscale evolution. The main advantage of using these concepts is the possibility of eliminating the approximations used in the standard approach by replacing complexity with fractality, that imposes, in mathematical terms, the mandatory use of the non-differential character of defined physical quantities. The theoretical model presented, validated for other physical systems, demonstrates its functionality also for drug delivery systems, highlighting, in addition, new insights into the complexity of this system. The spatio-temporal scales of system evolution are characterized through the fractality degree, as a measure of the complexity of the phenomena occurring at each scale. Numerical analysis of the experiment showed that the overall drug release kinetics can be obtained by composing "smaller release kinetics" occurring at scales appropriate for each phase of the drug release mechanism, phases whose expansion depends on the system density. Moreover, the uncertainties in establishing the exact limits of the phases were removed by applying the principle of scale superposition, resulting in a global fractality degree corresponding to the entire release kinetics. Even if the theoretical model is perfectible by identifying constants specific to each delivery system, this paper is intended to be the beginning of an alternative approach to drug delivery mechanisms.

摘要

在本文中,我们提出了一种针对药物递送系统动力学的新方法,该系统被视为复杂系统,此方法基于分形性、不可微性和多尺度演化等概念。使用这些概念的主要优势在于,通过用分形性取代复杂性,有可能消除标准方法中所使用的近似值,这在数学上强制规定了对定义的物理量使用不可微特性。所提出的理论模型已在其他物理系统中得到验证,它也证明了自身对药物递送系统的适用性,此外,还突出了对该系统复杂性的新见解。系统演化的时空尺度通过分形程度来表征,作为在每个尺度上发生的现象复杂性的一种度量。对实验的数值分析表明,总体药物释放动力学可以通过组合在适合药物释放机制各阶段的尺度上发生的“较小释放动力学”来获得,这些阶段的扩展取决于系统密度。此外,通过应用尺度叠加原理消除了确定各阶段精确界限时的不确定性,从而得到了与整个释放动力学相对应的全局分形程度。即使通过确定每个递送系统特有的常数可以使理论模型更加完善,但本文旨在成为药物递送机制替代方法的开端。

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