Nanobios Lab, Department of Bioscience and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
Academy of Medical Sciences, Pariyaram, Kerala 670503, India.
Mater Sci Eng C Mater Biol Appl. 2019 Feb 1;95:226-235. doi: 10.1016/j.msec.2018.10.080. Epub 2018 Oct 24.
Antibiotic resistance is of much prevalence and is one of the alarming realities for the rise in morbidity and mortality. Antibiotics; once regarded as wonder drugs have lost its credit of combating bacteria due to the rapid rise in variety of nosocomial pathogens. The underlying cause for the resistance spread is due to sudden drift in genetic mutation and the recalcitrant behavior of bacterial species. On the other hand, illegal and overconsumption of drugs fuels up the issue, wherein resistance development is directly proportional to the rate of drug consumption. Our pursuit was in reviving antibiotic, and further repurposing them into more potent formulation with reduced side effects to completely deplete resistant bacteria. In this work we present gentamicin encapsulated zein nanoparticle modified with Schiff base incorporated in immobilized chitosan-polyvinyl alcohol gel matrix([GM-ZNP]PG CsPVA) resulting in synergistic antibacterial activity. Schiff base modified zein nanoparticle exhibited an average diameter of 240 ± 8 nm and stability of -29.85 ± 2 mV. The nanocomposite system exhibited enhanced penetration rate when applied to dermis eliciting combinatorial antibacterial activity. Gentamicin in combination with Schiff base was found to lyse bacteria by ruining its cell integrity as depicted by SEM analysis. The formulation upon application stays intact to the impaired dermal tissues and releases drug in a sustained manner without the need of recurrent administration. The gel system was extremely biocompatible towards L929 cells without any toxicity. Overall, the work reports use of [GM-ZNP]PG CsPVA for resistant bacterial infections.
抗生素耐药性非常普遍,是发病率和死亡率上升的令人震惊的现实之一。抗生素曾经被视为神奇药物,但由于医院病原体种类的迅速增加,其对抗细菌的功效已经丧失。耐药性传播的根本原因是由于遗传突变的突然漂移和细菌物种的顽固行为。另一方面,非法和滥用药物加剧了这个问题,其中耐药性的发展与药物的消耗率直接成正比。我们的目标是重新利用抗生素,并进一步将其重新用于更有效的制剂,减少副作用,以彻底消灭耐药细菌。在这项工作中,我们提出了包封庆大霉素的玉米醇溶蛋白纳米颗粒,并用固定在壳聚糖-聚乙烯醇凝胶基质中的席夫碱进行修饰([GM-ZNP]PG CsPVA),从而产生协同抗菌活性。席夫碱修饰的玉米醇溶蛋白纳米颗粒的平均直径为 240 ± 8nm,稳定性为-29.85 ± 2mV。当应用于真皮时,纳米复合材料系统表现出增强的穿透率,产生组合抗菌活性。庆大霉素与席夫碱的组合被发现通过破坏其细胞完整性来裂解细菌,这一点可以通过 SEM 分析来描述。该制剂在应用时保持完整,不会对受损的皮肤组织造成伤害,并以持续的方式释放药物,无需反复给药。该凝胶系统对 L929 细胞具有极高的生物相容性,没有任何毒性。总的来说,这项工作报告了使用[GM-ZNP]PG CsPVA 治疗耐药性细菌感染。