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凝集素-细胞相互作用及其对肠道凝集素介导的药物递送的影响。

The lectin-cell interaction and its implications to intestinal lectin-mediated drug delivery.

作者信息

Gabor Franz, Bogner Elisabeth, Weissenboeck Andrea, Wirth Michael

机构信息

Institute of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.

出版信息

Adv Drug Deliv Rev. 2004 Mar 3;56(4):459-80. doi: 10.1016/j.addr.2003.10.015.

Abstract

Based on the fact that oligosaccharides encode biological information, the biorecognition between lectinised drug delivery systems and glycosylated structures in the intestine can be exploited for improved peroral therapy. Basic research revealed that some lectins can mediate mucoadhesion, cytoadhesion, and cytoinvasion of drugs. Entering the vesicular pathway by receptor mediated endocytosis, part of the conjugated drug is accumulated within the lysosomes. Additionally, part of the drug is supposed to be transported across the epithelium. Moreover, factors probably adversely influencing feasibility of the concept such as toxicity, immunogenicity, and intestinal stability of plant lectins are discussed. As exemplified by lectin-grafted prodrug and carrier systems, this strategy is expected to improve absorption and probably bioavailability of poorly absorbable drugs, peptides and proteins as well as therapeutic DNA.

摘要

基于寡糖编码生物信息这一事实,凝集素化药物递送系统与肠道中糖基化结构之间的生物识别可用于改善口服治疗。基础研究表明,一些凝集素可介导药物的粘膜粘附、细胞粘附和细胞侵袭。通过受体介导的内吞作用进入囊泡途径后,部分缀合药物会在溶酶体内积累。此外,部分药物应穿过上皮细胞进行转运。此外,还讨论了可能对该概念的可行性产生不利影响的因素,如植物凝集素的毒性、免疫原性和肠道稳定性。以凝集素嫁接前药和载体系统为例,该策略有望提高难吸收药物、肽和蛋白质以及治疗性DNA的吸收,并可能提高其生物利用度。

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