Poly(DL-lactic acid) scaffolds as a bone targeting platform for the co-delivery of antimicrobial agents against S. aureus-C.albicans mixed biofilms

Int J Pharm. 2022 Jun 25:622:121832. doi: 10.1016/j.ijpharm.2022.121832. Epub 2022 May 17.

Abstract

New strategies for the treatment of polymicrobial bone infections are required. In this study, the co-delivery of two antimicrobials by poly(D,L-lactic acid) (PDLLA) scaffolds was investigated in a polymicrobial biofilm model. PDLLA scaffolds were prepared by solvent casting/particulate leaching methodology, incorporating minocycline and voriconazole as clinically relevant antimicrobial agents. The scaffolds presented a sponge-like appearance, suitable to support cell proliferation and drug release. Single- and dual-species biofilm models of Staphylococcus aureus and Candida albicans were developed and characterized. S. aureus presented a higher ability to form single-species biofilms, compared to C. albicans. Minocycline and voriconazole-loaded PDLLA scaffolds showed activity against S. aureus and C. albicans single- and dual-biofilms. Ultimately, the cytocompatibility/functional activity of PDLLA scaffolds observed in human MG-63 osteosarcoma cells unveil their potential as a next-generation co-delivery system for antimicrobial therapy in bone infections.

Keywords: Bone infection; Co-delivery; Localized antibiotic delivery; Minocycline; Polymicrobial biofilms; Voriconazole.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents* / pharmacology
  • Biofilms
  • Candida albicans
  • Humans
  • Lactic Acid
  • Methicillin-Resistant Staphylococcus aureus*
  • Microbial Sensitivity Tests
  • Minocycline
  • Staphylococcus aureus
  • Voriconazole

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Lactic Acid
  • Minocycline
  • Voriconazole