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Colistin-loaded biodegradable nanoparticles as a promising antibacterial medication to reduce colistin-induced
Elena Sánchez-López1, Laura Guzman2, Roser Segovia3
1Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, Universitat de Barcelona (UB), Av. de Joan XXIII, 27-31, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), Universitat de Barcelona (UB), Av. Diagonal, 64, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Instituto de Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
Abstract:
Infectious diseases cause mortality rates over 17 million people per year. Among them, bacterial infections are one of the major causes. Nosocomial infections, including pneumonia and blood stream infections, are some of the most severe bacterial diseases and many of them display antimicrobial resistance. 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 deliver the drug in the site of the infection, improve its effectiveness and reduce the inherent toxicity, thus helping to overcome bacterial resistance. In this work, we aimed to encapsulate colistin sulfate, 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 adopted a round shape and a smooth surface. Besides, COL-NPs were able to release the drug in a sustained manner and showed suitable stability. In addition, in vitro assays confirmed that COL-NPs were effective against different gram-negative bacterial species such as Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii. Finally, in vivo experiments showed that COL-NPs did not induce 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.
Insights
Polymeric nanoparticles encapsulating colistin sulfate (COL-NPs) offer a promising solution for combating multi-drug resistant bacterial infections. These nanoparticles demonstrate efficacy and reduced toxicity in preclinical studies.
Area of Science:
- Nanomedicine
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Bacterial infections, particularly nosocomial ones, contribute significantly to global mortality.
- Increasing antimicrobial resistance poses a severe public health risk, necessitating novel therapeutic strategies.
- Nanomedicine offers a platform for targeted drug delivery, enhancing efficacy and reducing toxicity.
Purpose of the Study:
- To encapsulate colistin sulfate, an antibiotic for multi-drug resistant bacteria, into poly(lactic-co-glycolic) acid nanoparticles (COL-NPs).
- To characterize the physicochemical properties, stability, and drug release profile of COL-NPs.
- To evaluate the in vitro and in vivo efficacy and safety of COL-NPs.
Main Methods:
- Polymeric nanoparticles (COL-NPs) were synthesized encapsulating colistin sulfate.
- Physicochemical characterization included size, surface charge, morphology, and drug encapsulation.
- In vitro antibacterial activity against Gram-negative bacteria and in vivo toxicity and efficacy studies in mice were performed.
Main Results:
- Optimized COL-NPs exhibited a size below 200 nm, monodispersity, and negative surface charge.
- COL-NPs demonstrated sustained drug release, stability, and potent in vitro activity against Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii.
- In vivo studies showed reduced toxicity and improved safety profile compared to free colistin sulfate.
Conclusions:
- COL-NPs represent a viable nanomedicine approach for delivering colistin sulfate.
- COL-NPs effectively combat Gram-negative bacterial infections with reduced toxicity.
- This nanotechnology-based therapeutic strategy holds promise for addressing drug-resistant bacterial infections.
