Miconazole-splitomicin combined β-glucan hydrogel for effective prevention of Candida albicans periprosthetic joint

Menghan Wang1, Ying Yang2, Dongdong Li2

  • 1The first Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China; School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, , PR China.

Insights

A novel hydrogel combining splitomicin (SP) and miconazole nitrate (MCZ) effectively combats Candida albicans periprosthetic joint infections. This treatment inhibits fungal growth and biofilm formation, offering a promising solution for drug-resistant infections.

Area of Science:

  • Biomedical Engineering
  • Infectious Diseases
  • Materials Science

Background:

  • Periprosthetic joint infection (PJI) caused by Candida albicans (C. albicans) is a significant clinical challenge.
  • Biofilms formed by C. albicans contribute to antifungal resistance and treatment failure.
  • Novel therapeutic strategies are crucial for managing drug-resistant PJI.

Purpose of the Study:

  • To investigate the efficacy of splitomicin (SP) and miconazole nitrate (MCZ) in combination against C. albicans.
  • To develop and evaluate a β-glucan hydrogel for sustained delivery of SP and MCZ for PJI treatment.
  • To assess the in vivo therapeutic potential of the SP-MCZ-β-glucan hydrogel in a murine PJI model.

Main Methods:

  • Assessing the synergistic effects of SP and MCZ on C. albicans viability, proliferation, and morphology.
  • Incorporating SP and MCZ into a β-glucan hydrogel for controlled release.
  • Evaluating the hydrogel's performance in a murine model of C. albicans-induced PJI, focusing on implant colonization and tissue pathology.

Main Results:

  • SP inhibited C. albicans mycelial growth and enhanced MCZ sensitivity.
  • Combined SP and MCZ significantly reduced C. albicans viability, proliferation, yeast-to-hyphae transition, and biofilm formation.
  • The SP-MCZ-β-glucan hydrogel demonstrated sustained release properties and effectively reduced C. albicans colonization and femur damage in vivo.

Conclusions:

  • The combination of SP and MCZ shows potent antifungal activity against C. albicans.
  • SP-MCZ-β-glucan hydrogel is a promising drug delivery system for PJI management.
  • This novel hydrogel therapy holds potential for overcoming drug resistance in C. albicans PJI.