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Updated: Aug 11, 2026
A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials
Published on: March 3, 2023
In vitro and in vivo release of gentamicin from biodegradable discs
Pavan Kumar Naraharisetti1, Herman Chian Guan Lee, Yin-Chih Fu
1Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore.
Abstract:
Osteomyelitis is an infection of the bone and successful treatment involves the removal of the affected bone and the tissue by a surgical procedure following prolonged systemic and local antibiotic therapy for 4 to 6 weeks. The current local treatment is done by poly methyl methacrylate (PMMA) beads loaded with gentamicin and PMMA, being nondegradable, is to be removed by a second surgical procedure. The current study aims to develop a biodegradable composition that gives sustained release and hence reducing the need for a second surgery. Gentamicin-loaded discs were produced by compressing microparticle-gentamicin mixture obtained by spray drying a mixture of gentamicin in a solution of a biodegradable polymer. Different copolymers of poly (DL-lactic-co-glycolic acid) (PLGA) were used to study the effect of copolymer ratio and the hydrophilic-hydrophobic nature of the polymer. Theoretical drug loading up to 25% were studied and it was observed that 10% drug loading was optimum for gentamicin to be used as solid in spray drying. The results showed that about 60% of the drug is released in about 5 to 6 days and the remaining drug is released in about 30 days in total. An in vivo study was carried on rabbit femur and the local area and systemic concentration of gentamicin was monitored. It was observed that the local area concentration of gentamicin was above minimum inhibitory concentration for more than 20 days and this was also validated by computer simulations.
Insights
This study introduces a biodegradable gentamicin delivery system for osteomyelitis, reducing the need for a second surgery. The novel composition ensures sustained antibiotic release, maintaining therapeutic levels for over 20 days in vivo.
Area of Science:
- Biomaterials Science
- Infectious Diseases
- Drug Delivery Systems
Background:
- Osteomyelitis treatment requires prolonged antibiotic therapy and surgical removal of infected bone.
- Current local antibiotic delivery uses non-degradable polymethyl methacrylate (PMMA) beads, necessitating a second surgery for removal.
Purpose of the Study:
- To develop a biodegradable gentamicin-eluting composition for osteomyelitis treatment.
- To reduce the need for repeat surgical interventions by utilizing a sustained-release system.
Main Methods:
- Biodegradable gentamicin-loaded discs were fabricated using spray-dried microparticles of gentamicin within poly (DL-lactic-co-glycolic acid) (PLGA) copolymers.
- The effect of PLGA copolymer ratio and polymer hydrophilicity/hydrophobicity on drug release was investigated.
- In vivo studies in rabbit femur models assessed local and systemic gentamicin concentrations.
Main Results:
- Optimal gentamicin loading for spray drying was determined to be 10%.
- The biodegradable discs exhibited sustained gentamicin release, with approximately 60% released in 5-6 days and the remainder over 30 days.
- In vivo studies demonstrated gentamicin concentrations above the minimum inhibitory concentration (MIC) in the local area for over 20 days.
Conclusions:
- A biodegradable, sustained-release gentamicin delivery system was successfully developed for osteomyelitis.
- This novel approach has the potential to eliminate the requirement for a second surgery for implant removal.
- The developed system offers a promising alternative for localized, long-term antibiotic delivery in bone infections.
