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Amphotericin B delivery from bone cement increases with porosity but strength decreases
Chris Kweon1, Alex C McLaren, Christine Leon
1Banner Orthopaedic Residency, 901 E Wiletta, Phoenix, AZ 85006, USA.
Background:
Amphotericin B is a highly hydrophobic antifungal used for orthopaedic infections. There is disagreement about whether amphotericin B is released when it is loaded in polymethylmethacrylate (PMMA). It is unknown how much a poragen will increase amphotericin B release or decrease the compressive strength of the PMMA.
Questions/Purposes:
We therefore measured amphotericin B release and the compressive strength of amphotericin B loaded bone cement with and without adding high-dose poragen.
Methods:
Antifungal-loaded bone cement was formulated with Simplex P cement and 200 mg amphotericin B with and without 10 g cefazolin (poragen) per batch. Twenty standardized test cylinders were eluted in deionized water for each formulation. Cumulative amphotericin B mass and compressive strength were measured. Data were analyzed using repeated-measures analysis of variance.
Results:
Antifungal-loaded bone cement (ALBC) with 10 g poragen delivered more amphotericin B than ALBC containing amphotericin B alone by Day 15, 12.76 μg/cylinder (0.5%) versus 1.74 μg/cylinder (0.04%), respectively. With amphotericin B alone, compressive strength was unchanged and compressive strength did not decrease during elution. Adding 10 g poragen to ALBC with 200 mg amphotericin B decreased the compressive strength and compressive strength decreased further during elution, 80, 61, and 46 MPa at 0, 1, and 30 days, respectively.
Conclusions:
Amphotericin B is released in very small amounts from antifungal-loaded bone cement. Release can be increased by adding high-dose poragen, but compressive strength decreases sufficiently to limit its use for implant fixation.
Insights
Adding poragen to amphotericin B-loaded bone cement increases antifungal release but significantly reduces compressive strength. This limits its use for implant fixation due to compromised mechanical integrity.
Area of Science:
- Orthopaedic Surgery
- Biomaterials Science
- Pharmacology
Background:
- Amphotericin B, a hydrophobic antifungal, is used for orthopaedic infections.
- Debate exists regarding amphotericin B release from polymethylmethacrylate (PMMA).
- The impact of poragen on amphotericin B release and PMMA compressive strength is unclear.
Purpose of the Study:
- To quantify amphotericin B release from PMMA bone cement.
- To assess the effect of poragen on drug release and cement compressive strength.
- To determine the viability of poragen-enhanced antifungal delivery in bone cement.
Main Methods:
- Formulation of antifungal-loaded bone cement (ALBC) with amphotericin B and cefazolin (poragen).
- Elution of standardized test cylinders in deionized water.
- Measurement of cumulative amphotericin B release and compressive strength over time.
- Statistical analysis using repeated-measures analysis of variance.
Main Results:
- ALBC with poragen demonstrated significantly higher amphotericin B release (12.76 μg/cylinder) by Day 15 compared to ALBC without poragen (1.74 μg/cylinder).
- Amphotericin B alone did not alter compressive strength.
- Adding poragen markedly decreased compressive strength, with further reduction observed during elution (80 MPa to 46 MPa over 30 days).
Conclusions:
- Amphotericin B release from ALBC is minimal without poragen.
- High-dose poragen enhances amphotericin B release but compromises cement compressive strength.
- The significant decrease in mechanical integrity limits the clinical application of poragen-modified ALBC for implant fixation.
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