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Dual-Loaded Chitosan-Based Nanoparticles: A Novel approach for treating polymicrobial osteomyelitis.

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  • 1Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal; H&TRC - Centro de Investigação em Saúde e Tecnologia, ESTeSL - Escola Superior de Tecnologia da Saúde de Lisboa, IPL - Instituto Politécnico de Lisboa, Av. D. João II, Lote 4.69.01, 1990-096 Lisboa, Portugal.

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Summary

This study developed dual-loaded chitosan nanoparticles for osteomyelitis treatment. The nanoparticles effectively reduced polymicrobial biofilms, showing promise for treating complex bone infections.

Keywords:
Biofilm infectionsChitosanDrug delivery systemMinocyclineMinocycline hydrochlorideMixed osteomyelitis, polysaccharide nanoparticlesPoloxamerVoriconazole

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Infectious Diseases

Background:

  • Osteomyelitis caused by polymicrobial infections presents a significant therapeutic challenge.
  • Current treatments often struggle to effectively target both bacterial and fungal pathogens simultaneously.
  • Novel drug delivery systems are needed to improve treatment efficacy for complex bone infections.

Purpose of the Study:

  • To develop and characterize monodispersed chitosan nanoparticles co-loaded with minocycline (antibacterial) and voriconazole (antifungal).
  • To evaluate the in vitro anti-biofilm activity of the dual-loaded nanoparticles against polymicrobial osteomyelitis pathogens.
  • To assess the cytocompatibility of the nanoparticle system with human osteoblast cells.

Main Methods:

  • Preparation of monodispersed chitosan nanoparticles co-loaded with minocycline and voriconazole.
  • Encapsulation efficiency determination for both drugs.
  • Thermostability analysis to assess drug interactions within the nanoparticles.
  • In vitro anti-biofilm assays using Staphylococcus aureus and Candida albicans.
  • Cytotoxicity assays using a human osteoblast cell line.

Main Results:

  • Successful preparation of dual-loaded chitosan nanoparticles.
  • Minocycline exhibited higher encapsulation efficiency than voriconazole.
  • Thermostability analysis indicated potential interactions affecting voriconazole release.
  • Significant in vitro reduction (up to 90%) of polymicrobial biofilms.
  • Demonstrated cytocompatibility with human osteoblast cells.

Conclusions:

  • The developed chitosan nanoparticle system effectively co-delivers antibacterial and antifungal agents.
  • The dual-loaded nanoparticles show potent in vitro anti-biofilm activity against key osteomyelitis pathogens.
  • This system holds promise as an innovative therapeutic strategy for polymicrobial osteomyelitis.