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In vivo toxicity and biodistribution of intravenously administered antibiotic-functionalized gold nanoparticles

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Abstract

The utilization of engineered gold nanoparticles (GNPs) in biomedical applications is experiencing rapid growth owing to their reactive nature and remarkable flexibility. However, despite these advantages, concerns persist regarding their in vivo biocompatibility and cytotoxicity. This study aimed to assess the toxicity, biodistribution, and excretion pathways of GNPs functionalized with various antibiotics, namely, ciprofloxacin, levofloxacin, cefotaxime, and ceftriaxone, using a mouse model. Following intravenous administration, the nanostructures induced an increase in serum enzyme levels and histological abnormalities in the liver, indicating potential hepatotoxic effects. Analysis of organ distribution revealed accumulation primarily in the liver and spleen, with concentrations gradually decreasing 168-h post-administration. Fecal excretion was identified as the primary route of elimination, with a smaller portion excreted via urine. Among the different nanostructures evaluated, those functionalized with levofloxacin (LEV-NP) exhibited minimal organ toxicity and a high clearance rate. Additionally, LEV-NP, with a size of approximately 12 nm, demonstrated superior drug particle stability and lower red blood cell hemolytic activity compared to other nanostructures.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

The part of the study was supported by the Board of Research in Nuclear Sciences, Government of India (35/14/04/2014-BRNS).

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Authors and Affiliations

  1. Department of Biotechnology Engineering, NMAM Institute of Technology-Affiliated to NITTE (Deemed to Be University), Nitte, 574110, India

    Pradeepa, Darshini Shivamogga Mohan, Anil Kumar Honnali Srinivasalu & Vidya Shimoga Muddappa

  2. Department of Biotechnology, Sir M Visvesvaraya Institute of Technology, Bengaluru, 562157, India

    Rashmi Kanugodu Vasappa

  3. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, India

    Srinivas Mutalik

  4. Department of Biotechnology, Oxford College of Engineering, 10th Milestone, Hosur Road, Bangalore, 560068, India

    Manjunatha Bukkambudhi Krishnaswamy

  5. Department of Microbiology, S.R.N.M. National College of Applied Sciences, Kuvempu University, Shivamogga, 577201, India

    Mukunda Suryanarayana

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Contributions

Pradeepa carried out experiments, implementation, and methodology. He is involved in conceptualization, formal analysis, investigation, data collection, and writing of the original draft and performed statistical analysis. Rashmi KV is involved in writing of the original draft, formal analysis, supplementary material, data curation, and investigation. Darshini S. M is involved in writing of the original draft, editing the original draft, and supplementary material. Srinivas Mutalik contributed the resources and helped in supervision. Manjunatha B.K encouraged to investigate the designed experiments and supervised the finding of this work. Anil Kumar H.S helped to design the experiments and formal analysis. Mukunda S supported to develop methodology and encouraged to develop new inputs. Vidya S.M designed and planned the experiments and supervised in each steps and phases. She provided conceptualization, methodology, data curation, and formal analysis. She contributed to the interpretation of the results and verified the analytical methods. All authors reviewed the manuscript.

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Correspondence to Vidya Shimoga Muddappa.

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Pradeepa, Vasappa, R.K., Mohan, D.S. et al. In vivo toxicity and biodistribution of intravenously administered antibiotic-functionalized gold nanoparticles. Gold Bull 56, 209–220 (2023). https://doi.org/10.1007/s13404-024-00343-9

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