利用磁场优化药物洗脱支架的聚合物涂层厚度和支架宽度。

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-08-13 DOI:10.1016/j.ejpb.2024.114455
Seyed Masoud Vahedi, Jalel Azaiez
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引用次数: 0

摘要

利用有限体积法(FVM)对药物洗脱支架(DES)中存在磁场(MF)时药物/磁性颗粒(MP)共轭物的传输进行了数值模拟。通过研究组织渗透性、其各向异性和血浆粘度的作用,分析了不同钙化程度、药物颗粒大小和血细胞比容水平等生理条件的影响。研究发现,在没有 MF 和有 MF 的情况下,随着组织渗透性的降低或血浆粘度的增加,游离相药物和细胞外基质(ECM)结合相的含量都会增加。组织各向异性越强,自由相药物含量就越低,而与细胞外基质(ECM)结合相的含量就越高。在探讨的范围内,发现药物的特异性受体(SR)结合相对组织渗透性和血浆粘度不敏感,而且在各向异性组织中更大。激活 MF 会系统性地导致自由相药物含量增加,在组织渗透性、各向异性和血浆粘度较小的情况下,药物含量的增加最为显著。另一方面,在渗透性较大、血浆粘度较小和组织各向异性较低时,对 ECM 结合相含量的影响更大。对于各向同性组织,MF 在早期会导致 ECM 结合相含量减少,随后会增加。在考虑的渗透性和粘度范围内,MF 似乎不会对 SR 结合相产生任何明显影响。不过,在各向同性的组织中,药物的这一阶段往往会随着 MF 的激活而增加,而在各向异性的组织中则保持不变。据报道,MF 的这些作用有望缓解导致支架内再狭窄的两个因素,即聚合物涂层的宽度和厚度。研究表明,较窄或较薄的聚合物层与磁场纤维相结合,可以模拟较宽或较厚的聚合物层在没有磁场纤维的情况下的药物释放动态。我们确定了磁化支架的相应宽度和厚度(我们称之为等效聚合物宽度(EPW)和等效聚合物厚度(EPT)),并研究了它们与组织渗透性、各向同性和等离子体粘度的关系。研究结果表明,当使用 3A 的电流强度时,宽度或厚度只有非磁化支架一半的聚合物涂层可以达到相同的药物输送效果。
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Optimization of polymer coating thickness and strut width in drug Eluting stents using Magnetic field

The transport of drug/magnetic particle (MP) conjugates in the presence of a Magnetic Field (MF) in Drug Eluting Stents (DESs) is modeled numerically using the Finite Volume Method (FVM). The effects of physiological conditions corresponding to different degrees of calcification, drug particles sizes and hematocrit level, were analyzed by investigating the roles of the tissue permeability, its anisotropy and the plasma viscosity. It was found that both in the absence and presence of the MF, as the tissue permeability decreases or the plasma viscosity increases, the free-phase drug and Extracellular Matrix (ECM)-bound phase contents increase. Stronger tissue anisotropy leads to a decrease of the free-phase drug content and an increase of the ECM-bound phase content. Within the explored ranges, the Specific Receptor (SR)-bound phase of the drug was found to be insensitive to the tissue permeability and plasma viscosity, and to be larger in anisotropic tissues. The activation of the MF leads systematically to larger free-phase drug contents, with the increases most prominent at smaller tissue permeability, anisotropy and plasma viscosity. On the other hand, the effects on the ECM-bound phase content are found to be stronger at larger permeability, smaller plasma viscosity and lower tissue anisotropy. For an isotropic tissue, the MF induces a decrease of the ECM-bound phase content at early times, followed by an increase at later times. For the considered ranges of permeability and viscosity, the MF does not seem to have any noticeable effects on the SR-bound phase. However, this phase of the drug tends to increase with the activation of the MF in isotropic tissues and is unchanged in anisotropic ones. These reported effects of the MF hold promise for alleviating two factors contributing to In-Stent Restenosis, namely the polymer coating width and thickness. The study reveals that a narrower or thinner polymer layer, in combination with the MF, can mimic the drug release dynamics of a wider or thicker polymer layer in the absence of the MF. The corresponding width and thickness of the magnetized stents, that we referred to as the equivalent polymer width (EPW) and equivalent polymer thickness (EPT) were determined and their dependence on the tissue permeability, isotropy and the plasma viscosity, was investigated. The study shows that it is possible to achieve the same drug delivery with polymer coating of half the width or half the thickness of the non-magnetized stent when an electric intensity of 3A is used.

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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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