Department of Microbiology, BMS Block-I, Panjab University, Chandigarh 160014, India.
Department of Microbiology, BMS Block-I, Panjab University, Chandigarh 160014, India.
Int J Pharm. 2021 Feb 1;594:120175. doi: 10.1016/j.ijpharm.2020.120175. Epub 2020 Dec 16.
Developing non-antibiotic alternatives is one of the top priorities in healthcare and community settings, especially for combating biofilm-associated infections caused by multi-drug resistant pathogens. The therapeutic efficacy of nanolipoidal α-terpineol was explored against Pseudomonas aeruginosa induced keratitis using the mice model in the present study. Topical administration of nanostructured lipid carriers (NLCs) containing α-terpineol (αT) resulted in significant reduction in bacterial count in corneal tissue by 4 log on 5th post infection day. The protective efficacy of αT-NLCs demonstrated improvement in corneal histopathology, decreased the levels of various inflammatory markers including myeloperoxidase (MPO) and reactive nitrogen intermediates (RNI). Further, αT-NLCs treatment showed immunomodulatory effects by manipulating the production of inflammatory cytokines, tumor necrotic factor (TNF-α), macrophage inhibitory protein-2 (MIP-2) and interleukin-2 (IL-2) in infected eyes. In addition, ex vivo studies exhibited enhanced susceptibility of P. aeruginosa towards serum and macrophages in presence of αT-NLCs. A potent antibiofilm effect was also observed by αT-NLCs against P. aeruginosa which was confirmed by fluorescent microscopic analysis. Hence, based on the results of the present study, a novel therapeutic is being proposed for the treatment of biofilm associated keratitis caused by P. aeruginosa.
在医疗保健和社区环境中,开发非抗生素替代品是重中之重,特别是在对抗由多药耐药病原体引起的生物膜相关感染方面。本研究使用小鼠模型探索了纳米脂质体α-松油醇(αT)对铜绿假单胞菌诱导的角膜炎的治疗效果。局部给予含有αT 的纳米结构化脂质载体(NLC)可使感染后第 5 天角膜组织中的细菌数量减少 4 个对数级。αT-NLC 的保护效果显示出改善角膜组织病理学的作用,降低了髓过氧化物酶(MPO)和活性氮中间体(RNI)等各种炎症标志物的水平。此外,αT-NLC 治疗通过操纵感染眼中炎症细胞因子、肿瘤坏死因子-α(TNF-α)、巨噬细胞抑制蛋白-2(MIP-2)和白细胞介素-2(IL-2)的产生表现出免疫调节作用。此外,在存在αT-NLC 的情况下,体外研究显示铜绿假单胞菌对血清和巨噬细胞的敏感性增强。还观察到αT-NLC 对铜绿假单胞菌具有强大的抗生物膜作用,这通过荧光显微镜分析得到证实。因此,根据本研究的结果,提出了一种新的治疗方法,用于治疗由铜绿假单胞菌引起的生物膜相关角膜炎。