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Enzyme Degradable Polymersomes from Chitosan‐g‐[poly‐l‐lysine‐block‐ε‐caprolactone] Copolymer
Macromolecular Bioscience ( IF 4.6 ) Pub Date : 2020-12-02 , DOI: 10.1002/mabi.202000259
Yannick Bourgat 1 , Brigitte Tiersch 2 , Joachim Koetz 2 , Henning Menzel 1
Affiliation  

The scope of this study includes the synthesis of chitosan‐g‐[peptide‐poly‐ε‐caprolactone] and its self‐assembly into polymeric vesicles employing the solvent shift method. In this way, well‐defined core–shell structures suitable for encapsulation of drugs are generated. The hydrophobic polycaprolactone side‐chain and the hydrophilic chitosan backbone are linked via an enzyme‐cleavable peptide. The synthetic route involves the functionalization of chitosan with maleimide groups and the preparation of polycaprolactone with alkyne end‐groups. A peptide functionalized with a thiol group on one side and an azide group on the other side is prepared. Thiol‐ene click‐chemistry and azide–alkyne Huisgen cycloaddition are then used to link the chitosan and poly‐ε‐caprolactone chains, respectively, with this peptide. For a preliminary study, poly‐l‐lysin is a readily available and cleavable peptide that is introduced to investigate the feasibility of the system. The size and shape of the polymersomes are studied by dynamic light scattering and cryo‐scanning electron microscopy. Furthermore, degradability is studied by incubating the polymersomes with two enzymes, trypsin and chitosanase. A dispersion of polymersomes is used to coat titanium plates and to further test the stability against enzymatic degradation.

中文翻译:

壳聚糖-g- [聚-l-赖氨酸-嵌段-ε-己内酯]共聚物的可酶降解聚合物

这项研究的范围包括壳聚糖的合成[肽-聚-ε-己内酯]及其通过溶剂转移法自组装成聚合物囊泡。这样,就产生了适用于药物封装的定义明确的核-壳结构。疏水性聚己内酯侧链和亲水性壳聚糖主链通过酶切肽相连。合成途径包括将壳聚糖与马来酰亚胺基团官能化以及制备具有炔基端基的聚己内酯。制备了在一侧被巯基和在另一侧被叠氮基官能化的肽。然后使用巯基-点击化学和叠氮-炔烃Huisgen环加成法分别将壳聚糖和聚ε-己内酯链与该肽连接。对于一个初步的研究,聚溶血素是一种易于获得且可裂解的肽,被引入以研究该系统的可行性。通过动态光散射和低温扫描电子显微镜研究了聚合物小体的大小和形状。此外,通过将聚合体与两种酶(胰蛋白酶和壳聚糖酶)一起孵育来研究降解性。聚合物囊泡的分散体用于涂覆钛板,并进一步测试其抗酶促降解的稳定性。
更新日期:2021-01-16
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