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Release of different amphotericin B formulations from PMMA bone cements and their activity against Candida biofilm

Magdalena Czuban1, Dag Wulsten2, Lei Wang3

  • 1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Center for Musculoskeletal Surgery (CMSC), Germany; Freie Universität, Institute of Chemistry and Biochemistry, Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Germany.

Colloids and Surfaces. B, Biointerfaces
|August 12, 2019
PubMed

Insights

This study determined the optimal amphotericin B formulation for preventing fungal prosthetic joint infections. A minimum of 12.5 mg/g of non-liposomal amphotericin B is effective against Candida biofilms.

Area of Science:

  • Biomaterials Science
  • Mycology
  • Infectious Diseases

Background:

  • Polymethylmethacrylate (PMMA) bone cements are used for local delivery of amphotericin B to treat fungal prosthetic joint infections.
  • Optimal amphotericin B formulations and the impact of poragens in bone cements remain unclear.
  • Understanding these factors is crucial for effective treatment of Candida spp. infections.

Purpose of the Study:

  • To investigate the optimal amphotericin B formulation for preventing Candida biofilm formation in PMMA bone cements.
  • To evaluate the influence of different poragens, including gentamicin, on amphotericin B release and antifungal activity.
  • To determine the minimum effective concentration of amphotericin B in bone cement against various Candida species.

Main Methods:

  • Preparation and testing of various amphotericin B formulations (non-liposomal, liposomal, with/without gentamicin) incorporated into PMMA bone cement.
  • Assessment of antifungal activity against Candida albicans, C. glabrata, C. parapsilosis, and C. krusei biofilms using isothermal calorimetry and standard microbiological methods.
  • Measurement of cement compressive strength before and after antifungal elution.

Main Results:

  • Both sodium deoxycholate and N-methyl-D-glucamine/palmitate non-liposomal amphotericin B formulations demonstrated equivalent antifungal activity, with a minimum effective concentration of 12.5 mg/g against Candida biofilms.
  • Liposomal amphotericin B formulations showed increased drug release.
  • The addition of gentamicin reduced the release of sodium deoxycholate amphotericin B but could enhance release when combined with N-methyl-D-glucamine/palmitate amphotericin B.

Conclusions:

  • All tested amphotericin B formulations were effective against Candida biofilms, with 12.5 mg/g of non-liposomal drug being sufficient.
  • While compressive strength slightly decreased, it remained above recommended levels for implant fixation.
  • These findings offer valuable insights for optimizing the treatment of prosthetic joint infections caused by Candida species.
Keywords:
Amphotericin B-loaded bone cementBone cement spacerCandida biofilmFungal prosthetic joint infection

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