Resurrection of Nalidixic Acid: Evaluation of Water-Based Nanoformulations as Potential Nanomedicine

Abstract

Abstract Resistance to quinolone antibiotics has been a serious problem ever since nalidixic acid was introduced into clinical medicine. Over time, resistance of pathogenic microbes to nalidixic acid led to the design of novel variants to revive its potential application. In the present work, a series of eight nanoformulations of nalidixic acid-based diacyl and sulfonyl acyl hydrazine derivatives were prepared. All nanoformulations were found to be stable at different storage temperatures. Antibacterial and anticandida activity of the eight nanoformulations presented encouraging results when compared with their non-nano parent counterparts. The nanoformulations of chloro, furanyl, and sulfonyl acyl substituted derivatives of nalidixic acid displayed most promising results (MIC ranging from 50 to 100 μg mL−1) against the tested bacteria and yeast. Among the screened bacteria, Acinetobacter baumannii displayed maximum sensitivity to the above nanoformulations. Biosafety study on the mammalian model—wax moth, Galleria mellonella—showed that all eight prepared nanoformulations were absolutely nontoxic to the larvae and subsequent pupae and hence may likely have no or low toxicity against mammalian systems. Graphical Abstract

Keywords

• Nalidixic acid
• Antibiotics
• Hydrazine
• Nanoformulation
• Biosafety