【摘要】 目的 探讨pH敏感载体(PEPB_36/35)负载三氯生（TCS）的载药纳米粒(PEPB_36/35@TCS)清除耐甲氧西林金黄葡萄球菌（MRSA）生物被膜的作用。方法 采用纳米沉淀法制备pH敏感聚合物(PEPB_x/y),应用酸碱滴定法测定PEPB_x/y的解离常数（pKa）。通过激光共聚焦扫描显微镜考察PEPB_x/y清除MRSA生物被膜的效果，筛选出最优载体PEPB_36/35。通过纳米沉淀法制备PEPB_36/35@TCS,考察其药剂学性质。采用平板菌落计数法、结晶紫染色法和小鼠背部创面MRSA感染模型法，考察PEPB_36/35@TCS体内外清除MRSA生物被膜及内部细菌的能力。结果 PEPB_36/35的pKa值为5.6。PEPB_36/35的MRSA生物被膜清除率约为90%。PEPB_36/35@TCS的粒径为（190.6±4.05）nm,电位为（0.317±0.18）mV,多分散指数（PDI）为（0.172±0.017）。在酸性环境下，PEPB_36/35@TCS组的MRSA生物被膜内部细菌存活率、剩余生物被膜量以及创面细菌存活率均显著降低（P<0.01）。结论 PEPB_36/35@TCS在酸性环境下具有较好的清除MRSA生物被膜及内部细菌的效果，可以发挥促进感染创面愈合的作用。更多还原

【Abstract】 Objective To investigate the efficacy of pH-sensitive carrier(PEPB_36/35) loaded with triclosan（TCS） in the form of drug-loaded nanoparticles(PEPB_36/35@TCS) for the eradication of Methicillin-resistant Staphylococcus aureus（MRSA） biofilms.Methods pH-sensitive polymers(PEPB_x/y) were prepared by using nanoprecipitation techniques. The dissociation constant（pKa） of PEPB_x/y were determined through acid-base titration. The effectiveness of PEPB_x/y in eradicating MRSA biofilms were examined by using Confocal Laser Scanning Microscopy, from which the optimal carrier PEPB_36/35 was selected. PEPB_36/35@TCS was prepared by using nanoprecipitation and its pharmacological properties were examined. The in vitro and in vivo efficacy of PEPB_36/35@TCS in eradicating MRSA biofilms and internal bacteria were assessed by using agar plate colony counting, crystal violet staining, and mouse dorsal wound MRSA infection model.Results The pKa value of PEPB_36/35 was found to be 5.6. The MRSA biofilm eradication rate by PEPB_36/35 was approximately 90%. The particle size of PEPB_36/35@TCS was（190.6±4.05） nm, with a zeta potential of（0.317±0.18） mV and a Polydispersity Index（PDI） of（0.172±0.017）. In acidic environments, the survival rate of MRSA biofilm internal bacteria, residual biofilm mass, and wound bacteria survival rate significantly reduced（P<0.01） in the PEPB_36/35@TCS group.Conclusion PEPB_36/35@TCS demonstrated effective eradication of MRSA biofilms and internal bacteria in acidic environments, and can play a role in promoting the healing of infected wounds.更多还原