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支链两性霉素功能化聚(丙烯酰胺丙酯):一种抗真菌聚合物。

Branched amphotericin functional poly(-propyl acrylamide): an antifungal polymer.

作者信息

Swift Thomas, Caseley Emily, Pinnock Abbigail, Shepherd Joanna, Shivshetty Nagaveni, Garg Prashant, Ian Douglas C W, MacNeil Sheila, Rimmer Stephen

机构信息

Polymer and Biomaterial Chemistry Laboratories, School of Chemistry and Biosciences, University of Bradford, Bradford BD7 1DP, UK.

School of Dentistry, University of Sheffield, Sheffield S10 2TA, UK.

出版信息

R Soc Open Sci. 2021 Jan 13;8(1):201655. doi: 10.1098/rsos.201655. eCollection 2021 Jan.

Abstract

Branched poly(-propylacrylamide) was functionalized with Amphotericin B (AmB) at the chain ends to produce an antifungal material. The polymer showed antifungal properties against AmB-sensitive strains of , and (minimal inhibitory concentration ranged from 5 to 500 µg ml) but was not effective against an AmB resistant strain of nor against . The polymer end groups bound to the AmB target, ergosterol, and the fluorescence spectrum of a dye used as a solvatochromic probe, Nile red, was blue shifted indicating that segments of the polymer became desolvated on binding. The polymer was less toxic to corneal and renal epithelial cells and explanted corneal tissue than the free drug. Also, the polymer did not induce reactive oxygen species release from peripheral blood mononuclear cells, nor did it cause a substantial release of the proinflammatory cytokines, tumour necrosis factor-α and interleukin-1 (at 0.5 mg ml).

摘要

将两性霉素B(AmB)连接到支链聚(-丙基丙烯酰胺)的链端,以制备一种抗真菌材料。该聚合物对AmB敏感的白色念珠菌、热带念珠菌和近平滑念珠菌菌株具有抗真菌特性(最低抑菌浓度范围为5至500μg/ml),但对AmB耐药的白色念珠菌菌株和光滑念珠菌无效。聚合物端基与AmB的靶点麦角固醇结合,用作溶剂化显色探针的染料尼罗红的荧光光谱发生蓝移,表明聚合物链段在结合时去溶剂化。与游离药物相比,该聚合物对角膜和肾上皮细胞以及离体角膜组织的毒性较小。此外,该聚合物不会诱导外周血单核细胞释放活性氧,也不会导致促炎细胞因子肿瘤坏死因子-α和白细胞介素-1大量释放(浓度为0.5mg/ml时)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b62d/7890487/b3d73b0bef15/rsos201655-g1.jpg

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