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Enzyme decorated drug carriers: Targeted swords to cleave and overcome the mucus barrier
Advanced Drug Delivery Reviews ( IF 16.1 ) Pub Date : 2017-10-24 , DOI: 10.1016/j.addr.2017.10.004
Claudia Menzel , Andreas Bernkop-Schnürch

The use of mucus permeating drug carrier systems being able to overcome the mucus barrier can lead to a remarkable enhancement in bioavailability. One promising approach is the design of mucolytic enzyme decorated carrier systems (MECS). These systems include micro- and nanoparticles as well as self-emulsifying drug delivery systems (SEDDS) decorated with mucin cleaving enzymes such as papain (PAP) or bromelain (BRO). MECS are able to cross the mucus barrier in a comparatively efficient manner by cleaving mucus substructures in front of them on their way to the epithelium. Thereby these enzymes hydrolyze peptide bonds of mucus glycoproteins forming tiny holes or passages through the mucus. In various in vitro and in vivo studies MECS proved to be superior in their mucus permeating properties over nanocarriers without enzyme decoration. PAP decorated nanoparticles, for instance, remained 3 h after oral administration to an even 2.5-fold higher extend in rat small intestine than the corresponding undecorated nanoparticles permeating the intestinal mucus gel layer to a much lower degree. As MECS break up the mucus network only locally without destroying its overall protective barrier function, even long term treatments with such systems seem feasible.

Within this review article we address different drug carrier systems decorated with various types of enzymes, their particular pros and cons and potential applications.



中文翻译:

酶修饰的药物载体:靶向的剑可劈开并克服粘液屏障

使用能够克服粘液屏障的粘液渗透性药物载体系统可以导致生物利用度的显着提高。一种有前途的方法是粘液溶解酶修饰的载体系统(MECS)的设计。这些系统包括微颗粒和纳米颗粒,以及用诸如木瓜蛋白酶(PAP)或菠萝蛋白酶(BRO)的粘蛋白裂解酶修饰的自乳化药物递送系统(SEDDS)。MECS能够通过在粘液亚结构到达上皮的过程中在它们前面裂解粘液亚结构,从而以相对有效的方式穿过粘液屏障。因此,这些酶水解粘液糖蛋白的肽键,形成穿过粘液的小孔或通道。在各种体外和体内研究中,证明MECS的粘液渗透性能优于没有酶修饰的纳米载体。例如,PAP修饰的纳米颗粒在口服后3小时仍保留在大鼠小肠中,其延伸程度要比渗透到肠道粘液凝胶层的相应未经修饰的纳米颗粒低得多,甚至高出2.5倍。由于MECS仅在局部破坏粘液网络而不破坏其整体保护屏障功能,因此即使使用此类系统进行长期治疗似乎也是可行的。

在这篇评论文章中,我们讨论了装饰有各种类型酶的不同药物载体系统,它们的优缺点和潜在应用。

更新日期:2017-10-24
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