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A calcium sulphate/hydroxyapatite ceramic biomaterial carrier for local delivery of tobramycin in bone infections : Analysis of rheology, drug release and antimicrobial efficacy

Huang, Jintian LU ; Sebastian, Sujeesh LU orcid ; Collin, Mattias LU orcid ; Tägil, Magnus LU ; Lidgren, Lars LU and Raina, Deepak Bushan LU (2023) In Ceramics International 49(21). p.33725-33734
Abstract

Local targeted treatment of bone and joint infections using antibiotic-containing carriers is a common practice today. A recently FDA approved biphasic calcium sulphate/hydroxyapatite (CaS/HA) carrier containing gentamicin has been reported to give a sustained drug release, highly effective in eradicating bone infections. We present the first study evaluating the widely used aminoglycoside tobramycin (TOB) incorporated in the CaS/HA material with or without gentamycin (GEN) or vancomycin (VAN) with focus on rheology, drug release and antibacterial efficacy. In-vitro antibiotic release kinetics and biomaterial degradation were established by immersing the composites in phosphate buffered saline. The anti-bacterial effect of antibiotic... (More)

Local targeted treatment of bone and joint infections using antibiotic-containing carriers is a common practice today. A recently FDA approved biphasic calcium sulphate/hydroxyapatite (CaS/HA) carrier containing gentamicin has been reported to give a sustained drug release, highly effective in eradicating bone infections. We present the first study evaluating the widely used aminoglycoside tobramycin (TOB) incorporated in the CaS/HA material with or without gentamycin (GEN) or vancomycin (VAN) with focus on rheology, drug release and antibacterial efficacy. In-vitro antibiotic release kinetics and biomaterial degradation were established by immersing the composites in phosphate buffered saline. The anti-bacterial effect of antibiotic containing CaS/HA composites as well as antibiotics release fractions were evaluated by Kirby-Bauer disk diffusion against S. aureus. The CaS/HA + GEN + TOB combination delayed setting to over 30 min whereas TOB + VAN slightly prolonged setting time (25 min vs. 15 min) still with good injectability. TOB was released from CaS/HA continuously for 35 days and during this period, the antibiotic loaded biomaterial could show a continuous anti-bacterial efficacy even at the last time point of day-35. After day-35, the pellets used for antibiotic release were taken out from release medium and broken into a paste. CaS/HA + TOB paste showed the largest ZOI (25 mm) against S. aureus ATCC 25923, while CaS/HA + VAN paste had no ZOI and CaS/HA + VAN + TOB paste had a ZOI of 18 mm. At the same time, the ZOI of CaS/HA + TOB against S. aureus P-3 was 14 mm compared to 0 mm in the other two groups. Adding TOB to CaS/HA containing VAN, extended the antimicrobial effect with a longer time and larger zone of inhibition, while no synergistic effect of the co-delivery was observed. Our in-vitro results indicate that CaS/HA could be used as a carrier for TOB as a local targeted delivery system in the treatment of bone infections.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomaterial, Bone, Calcium sulphate/hydroxyapatite, Infection, Tobramycin, Vancomycin
in
Ceramics International
volume
49
issue
21
pages
33725 - 33734
publisher
Elsevier
external identifiers
  • scopus:85168322203
ISSN
0272-8842
DOI
10.1016/j.ceramint.2023.08.064
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 The Authors
id
b2d0809e-12c8-450e-aa6c-ecd00c8928e1
date added to LUP
2023-08-28 14:11:13
date last changed
2023-10-26 14:46:06
@article{b2d0809e-12c8-450e-aa6c-ecd00c8928e1,
  abstract     = {{<p>Local targeted treatment of bone and joint infections using antibiotic-containing carriers is a common practice today. A recently FDA approved biphasic calcium sulphate/hydroxyapatite (CaS/HA) carrier containing gentamicin has been reported to give a sustained drug release, highly effective in eradicating bone infections. We present the first study evaluating the widely used aminoglycoside tobramycin (TOB) incorporated in the CaS/HA material with or without gentamycin (GEN) or vancomycin (VAN) with focus on rheology, drug release and antibacterial efficacy. In-vitro antibiotic release kinetics and biomaterial degradation were established by immersing the composites in phosphate buffered saline. The anti-bacterial effect of antibiotic containing CaS/HA composites as well as antibiotics release fractions were evaluated by Kirby-Bauer disk diffusion against S. aureus. The CaS/HA + GEN + TOB combination delayed setting to over 30 min whereas TOB + VAN slightly prolonged setting time (25 min vs. 15 min) still with good injectability. TOB was released from CaS/HA continuously for 35 days and during this period, the antibiotic loaded biomaterial could show a continuous anti-bacterial efficacy even at the last time point of day-35. After day-35, the pellets used for antibiotic release were taken out from release medium and broken into a paste. CaS/HA + TOB paste showed the largest ZOI (25 mm) against S. aureus ATCC 25923, while CaS/HA + VAN paste had no ZOI and CaS/HA + VAN + TOB paste had a ZOI of 18 mm. At the same time, the ZOI of CaS/HA + TOB against S. aureus P-3 was 14 mm compared to 0 mm in the other two groups. Adding TOB to CaS/HA containing VAN, extended the antimicrobial effect with a longer time and larger zone of inhibition, while no synergistic effect of the co-delivery was observed. Our in-vitro results indicate that CaS/HA could be used as a carrier for TOB as a local targeted delivery system in the treatment of bone infections.</p>}},
  author       = {{Huang, Jintian and Sebastian, Sujeesh and Collin, Mattias and Tägil, Magnus and Lidgren, Lars and Raina, Deepak Bushan}},
  issn         = {{0272-8842}},
  keywords     = {{Biomaterial; Bone; Calcium sulphate/hydroxyapatite; Infection; Tobramycin; Vancomycin}},
  language     = {{eng}},
  number       = {{21}},
  pages        = {{33725--33734}},
  publisher    = {{Elsevier}},
  series       = {{Ceramics International}},
  title        = {{A calcium sulphate/hydroxyapatite ceramic biomaterial carrier for local delivery of tobramycin in bone infections : Analysis of rheology, drug release and antimicrobial efficacy}},
  url          = {{http://dx.doi.org/10.1016/j.ceramint.2023.08.064}},
  doi          = {{10.1016/j.ceramint.2023.08.064}},
  volume       = {{49}},
  year         = {{2023}},
}