Dual Transport of Active Substances with a Layer-by-Layer-Based Drug Delivery System to Terminate Inflammatory Processes.,Macromolecular Bioscience

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Dual Transport of Active Substances with a Layer-by-Layer-Based Drug Delivery System to Terminate Inflammatory Processes.
Macromolecular Bioscience ( IF 4.4 ) Pub Date : 2020-07-06 , DOI: 10.1002/mabi.202000097
Mandy Brueckner ₁ , Sebastian Hollenbach-Latzko ₁ , Uta Reibetanz ₁

Affiliation

Conventional therapies for chronic inflammation with high dose application of active agents are often accompanied with severe side effects so that other therapeutical strategies shall be developed to be less physically demanding but still highly efficient. Locally applied Layer‐by‐Layer (LbL) microcarriers transporting a low, but efficient dosage of active agents directly into the inflamed tissue offer a gentle therapy option. Here, the inhibition of highly degradative enzyme human neutrophile elastase (HNE) is adressed, which is produced and secreted by neutrophile granulocytes (PMNs) in the progress of inflammation. The protected transport and release of its natural inhibitor α1‐antitrypsin (AT) as a constituent of the microcarrier's biopolymer multilayer allows for an efficient inhibition of extra‐ and intracellular elastase. The HOCl scavenger molecule cefoperazone, which preserves AT activity, as an additional multilayer constituent induces a much higher efficacy of the inhibitor. The successful assembly of both agents in different layers of the multilayer and the subsequent HNE inhibition in PMNs is investigated. The parallel application of cefoperazone leads to an enhanced inhibitory effect even with reduced AT amount and reduced carrier:cell ratio. It is demonstrated that the modular assembly strategy of LbL carriers allows for efficient synergistic effect of active agents in inflammatory process.

中文翻译：

活性物质的双重传输与基于逐层的药物递送系统以终止炎症过程。

使用高剂量活性剂治疗慢性炎症的常规疗法往往伴随着严重的副作用，因此应开发其他治疗策略以减少对体力的要求但仍然高效。局部应用的逐层 (LbL) 微载体将少量但有效剂量的活性剂直接输送到发炎组织中，提供了一种温和的治疗选择。在这里，高度降解酶人中性粒细胞弹性蛋白酶 (HNE) 的抑制得到了解决，HNE 是在炎症过程中由中性粒细胞 (PMN) 产生和分泌的。其天然抑制剂α1-抗胰蛋白酶（AT）作为微载体生物聚合物多层的组成部分的受保护运输和释放允许有效抑制细胞外和细胞内弹性蛋白酶。HOCl 清除剂分子头孢哌酮保留了 AT 活性，作为额外的多层成分可诱导更高的抑制剂功效。研究了两种药剂在多层的不同层中的成功组装以及随后在 PMN 中的 HNE 抑制。头孢哌酮的平行应用导致增强的抑制作用，即使 AT 量减少和载体：细胞比降低。结果表明，LbL 载体的模块化组装策略允许活性剂在炎症过程中产生有效的协同作用。研究了两种药剂在多层的不同层中的成功组装以及随后在 PMN 中的 HNE 抑制。头孢哌酮的平行应用导致增强的抑制作用，即使 AT 量减少和载体：细胞比降低。结果表明，LbL 载体的模块化组装策略允许活性剂在炎症过程中产生有效的协同作用。研究了两种药剂在多层的不同层中的成功组装以及随后在 PMN 中的 HNE 抑制。头孢哌酮的平行应用导致增强的抑制作用，即使 AT 量减少和载体：细胞比降低。结果表明，LbL 载体的模块化组装策略允许活性剂在炎症过程中产生有效的协同作用。

更新日期：2020-07-06

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