Bhardwaj Snigdha, Bhatia Sonam, Gupta Pushpraj S, Singh Shaminder
Department of Pharmaceutical Science, SHALOM Institute of Health and Allied Sciences, Sam Higginbottom University of Agriculture.
Technology and Sciences (SHUATS), Naini, Prayagraj, India.
Iran J Basic Med Sci. 2022 Mar;25(3):352-363. doi: 10.22038/IJBMS.2022.59419.13192.
Antimicrobial resistance emerged as a global challenge owing to limited therapeutic options to control infections. , an MDR pathogen already developed resistance against many conventional antibiotics. An "anti-virulence strategy" that targets bacterial virulence rather than growth proves effective against drug-resistant pathogens.
Here, we used a structure-based drug design approach to identify lead molecules using the LasR receptor protein of as a target responsible for virulence production in this bacterium. From the identified hits, we developed lead-based nanoformulation and investigated its effectiveness for treating the associated surface-infection . First, TC-based nanoemulsions were fabricated by high-pressure homogenization and evaluated for various parameters. The optimized nanoemulsions were thereby utilized to prepare NEG.
The nanoemulsion (F3) exhibited low droplet size (51.04±1.88 nm), PDI (0.065±1.14), and negative zeta potential (-33.65±0.82 mV). In animals, topical application of NEG-3 demonstrated significant improvement on skin permeability (459±10.17 µg), drug influx (18.99±0.76 μg/cm hr), and repressed the CFU of induced-surface infection (≤ 0.001). The histology of rat skin demonstrated a significant effect for groups treated with TC-based NEGs as compared with a negative control group, whereas no significant effect was seen on rat liver indicating low systemic exposure to the drug. Also, NEG3 showed no significant changes under different stability conditions after 3 months.
TC-based NEGs open up the possibility of a more effective way to combat serious surface infections caused by
由于控制感染的治疗选择有限，抗菌药物耐药性已成为一项全球性挑战。 ，一种多重耐药病原体已经对许多传统抗生素产生了耐药性。一种针对细菌毒力而非生长的“抗毒力策略”已被证明对耐药病原体有效。
在此，我们采用基于结构的药物设计方法，以 菌的LasR受体蛋白为靶点来鉴定先导分子，该靶点负责该细菌的毒力产生。从鉴定出的活性化合物中，我们开发了基于先导物的纳米制剂，并研究了其治疗 菌相关表面感染的有效性。首先，通过高压均质法制备了基于吐温80的纳米乳剂，并对其各种参数进行了评估。从而利用优化后的纳米乳剂制备了纳米乳凝胶。
纳米乳剂（F3）呈现出低液滴尺寸（51.04±1.88 nm）、多分散指数（0.065±1.14）和负的zeta电位（-33.65±0.82 mV）。在动物实验中，局部应用纳米乳凝胶-3在皮肤通透性（459±10.17 μg）、药物流入量（18.99±0.76 μg/cm·hr）方面有显著改善，并抑制了 菌诱导的表面感染的菌落形成单位（≤0.001）。大鼠皮肤组织学检查表明，与阴性对照组相比，基于吐温80的纳米乳凝胶处理组有显著效果，而对大鼠肝脏无显著影响，表明药物的全身暴露量较低。此外，纳米乳凝胶3在3个月的不同稳定性条件下没有显著变化。
基于吐温80的纳米乳凝胶为对抗由 菌引起的严重表面感染开辟了一种更有效的途径的可能性
