Enhanced Antibacterial Efficacy of Bioceramic Implants Functionalized with Ciprofloxacin: An In Silico and In Vitro Study

Author:

Văruț Renata-Maria1,Rotaru Luciana Teodora2ORCID,Cimpoesu Diana3ORCID,Corlade Mihaela3,Singer Cristina Elena4,Popescu Alin Iulian Silviu5,Popescu Cristina6ORCID,Iulian-Nicolae Iliescu4ORCID,Mocanu Adriana7,Popescu Mihaela8,Butoi Mihai Alexandru2,Nicolaescu Oana Elena9ORCID

Affiliation:

1. Research Methodology Department, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania

2. Emergency Medicine and First Aid Department, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania

3. Emergency St. Spiridon Hospital, Faculty of Medicine, University of Medicine and Pharmacy Gr. T. Popa, 700115 Iasi, Romania

4. Department of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania

5. Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania

6. Department of Anatomy, University of Medicine and Pharmacy, Discipline of Anatomy, 200349 Craiova, Romania

7. Pharmacist at the Military Emergency Clinical Hospital, 200749 Craiova, Romania

8. Department of Endocrinology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania

9. Department of Pharmaceutical Technique, University of Medicine and Pharmacy, Discipline of Anatomy, 200349 Craiova, Romania

Abstract

This study explores the antibacterial efficacy and cytotoxicity of ciprofloxacin-functionalized bioceramic implants. We synthesized hydroxyapatite-ciprofloxacin (HACPXCS) composites and applied them to titanium substrates (Ti-HA-CPX), evaluating their performance in vitro against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922). Antibacterial activity was assessed using the Kirby-Bauer disc diffusion method, while cytotoxicity was tested using mesenchymal stem cells. The results demonstrated that Ti-HA-CPX exhibited superior antibacterial activity, with inhibition zones of 33.5 mm (MIC 0.5 µg/mL) for Staphylococcus aureus (ATCC 25923) and 27.5 mm (MIC 0.25 µg/mL) for Escherichia coli (ATCC 25922). However, Ti-HA-CPX showed moderate cytotoxicity (80% cell viability). HACPXCS composites, whether chemically synthesized or mechanically mixed (HACPXMM), also displayed significant antibacterial activity, but with cytotoxicity ranging from low to moderate levels. Molecular docking studies confirmed strong binding affinities between ciprofloxacin and bacterial proteins, correlating with enhanced antibacterial efficacy. These findings suggest that Ti-HA-CPX composites offer a promising approach for single-stage surgical interventions in treating chronic osteomyelitis and infected fractures, balancing antibacterial effectiveness with manageable cytotoxicity.

Funder

University of Medicine and Pharmacy of Craiova, Romania

Publisher

MDPI AG

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