Colistin-loaded biodegradable nanoparticles as a promising antibacterial medication to reduce colistin-induced toxicity

Abstract

Infectious diseases cause mortality rates over 17 million people per year. Among them, bacterial infections constitute one of the major causes. Pneumonia and nosocomial infections are the most severe bacterial infections. Moreover, the indiscriminate use of antibiotics during the last decades has triggered an increasing multiple resistance towards these drugs, which represents a serious global socioeconomic and public health risk. In this sense, nanomedicine has provided an innovative therapeutic alternative able to accumulate the drug in the site of the infection, improve its effectiveness and reduce the inherent toxicity, thus leading to overcoming bacterial resistance. In this work, we aimed to encapsulate colistin, an antibiotic commonly used against multi-drug resistant bacteria in polymeric nanoparticles of poly(lactic-co-glycolic) acid (COL-NPs). COL-NPs were optimized obtaining an average size below 200 nm, monodisperse population and a negative surface charge. Physicochemical assays confirmed that the drug was encapsulated into the polymeric matrix and COL-NPs possessed a round shape and a smooth surface. Moreover, COL-NPs were able to release the drug in a sustained manner and showed suitable stability. In addition, <em>in vitro</em> assays confirmed that COL-NPs were effective against different gram-negative bacterial species such as <em>Pseudomonas aeruginosa</em>, <em>Escherichia coli</em> and <em>Acinetobacter baumannii</em>. Finally, <em>in vivo</em> experiments showed that COL-NPs did not promote any toxicological effects in treated mice, reducing renal concentrations compared to the free drug, maintaining urea levels comparable to those of the control group, and decreasing most of the colistin-induced neurotoxic effects. All these results together suggest that COL-NPs could be a promising therapeutic tool against drug-resistant bacterial infections.