针对伤口病原体的抗微生物光谱和基于聚氨酸的抗微生物聚合物的星排列细胞毒性
Aaron Doherty1,2,3, Robert Murphy4, Andreas Heise4
1Department of Clinical Microbiology, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
Journal of medical microbiology
|September 13, 2024
概括
一种基于聚-l-氨酸 (PLL) 的新型抗微生物 (AMP) 聚合物显示出针对ESKAPE病原体的广泛杀菌活性. 然而,由于对人体细胞具有显著的毒性,不建议进一步开发这种特定的AMP.
科学领域:
- 生物材料科学 生物材料科学
- 抗微生物是一种抗菌.
- 伤口感染管理 伤口感染管理
背景情况:
- 越来越多的患者群体面临感染风险的增加,需要用于伤口管理的新型局部广泛抗微生物药物.
- 对抗微生物 (AMP) 的细胞毒性和活性谱的强有力的临床前评估至关重要,但往往缺乏.
- 基于聚-l-氨酸 (PLL) 的AMP聚合物代表了开发新抗菌剂的一个有希望的领域.
研究的目的:
- 为了评估16臂星AMP聚合物的体外杀菌活性,16-PLL10.
- 评估16-PLL10对人类角质细胞和红细胞的细胞毒性.
- 探索对16-PLL10进行修改,以提高其安全性.
主要方法:
- 16-PLL10对ESKAPE病原体 (临床分离物和参考菌株) 的抗菌敏感性测试.
- 在体外测试人类红细胞血解和角质细胞活性的测试,以确定细胞毒性.
- 合成和评估经过修改的16-PLL10结合物 (TFA和PEG-ylated) 以减轻毒性.
主要成果:
- 16-PLL10对ESKAPE菌株具有广泛的杀菌活性,最小的杀菌度从1.25μM到≥25μM不等.
- 在有效度下,16-PLL10对人类角质细胞和红细胞具有显著的毒性.
- 修改后的结合物 (TFA和PEG-化16-PLL10) 仅对细胞毒性和血液溶解有适度的降低.
结论:
- 16-PLL10的不良选择性指数表明,该特定聚合物的进一步开发不太可能是合理的.
- 简单的合成和修改AMP聚合物对于解决未满足的新型局部抗菌素需求仍然具有吸引力.
- 未来的AMP开发应该优先考虑使用临床相关的病原体和人体细胞进行体外表征,以建立选择性毒性概况,AI和计算查可能会加速.
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