TY - JOUR
T1 - Gentamicin extended release from an injectable polymeric implant
AU - Krasko, Michal Y.
AU - Golenser, Jacob
AU - Nyska, Abraham
AU - Nyska, Meir
AU - Brin, Yaron S.
AU - Domb, Abraham J.
PY - 2007/1/22
Y1 - 2007/1/22
N2 - Gentamicin sulfate, a potent antibiotic agent, is currently used for treatment of osteomyelitis mainly by intravenous injection with a long-term indwelling catheter, local implant of antibiotic containing polymethylmethacrylate beads or calcium phosphate (bone cements). Searching for more effective treatments, this study was designed to evaluate biodegradable injectable gelling polymeric devices for the controlled release of gentamicin sulfate in the treatment of invasive bacterial infections. Gentamicin sulfate was incorporated in poly(sebacic-co-ricinoleic-ester-anhydride P(SA-RA)) paste at 10-20% w/w and its release in buffer solution was monitored. The in vitro activity of the formulations was determined against Staphylococcus aureus. A constant release of active gentamicin for over 28 days was found. The stability of the formulation was determined under different storage conditions. The formulations were stable to sterilization by γ-irradiation and long term storage under freezing. The toxicity of the polymer and the formulations with gentamicin was examined by subcutaneous injection to rats. Four weeks after implantation, histopathological examination of the tissues surrounding the implant showed no inflammation. A preliminary study revealed positive effect of gentamicin containing P(SA-RA) on established osteomyelitis in a rat model. In conclusion this study suggests that poly(sebacic-co-ricinoleic-ester-anhydride) 3:7 loaded with 10%-20% gentamicin sulfate, might be used as an injectable biodegradable device for in situ treatment of osteomyelitis induced by S. aureus.
AB - Gentamicin sulfate, a potent antibiotic agent, is currently used for treatment of osteomyelitis mainly by intravenous injection with a long-term indwelling catheter, local implant of antibiotic containing polymethylmethacrylate beads or calcium phosphate (bone cements). Searching for more effective treatments, this study was designed to evaluate biodegradable injectable gelling polymeric devices for the controlled release of gentamicin sulfate in the treatment of invasive bacterial infections. Gentamicin sulfate was incorporated in poly(sebacic-co-ricinoleic-ester-anhydride P(SA-RA)) paste at 10-20% w/w and its release in buffer solution was monitored. The in vitro activity of the formulations was determined against Staphylococcus aureus. A constant release of active gentamicin for over 28 days was found. The stability of the formulation was determined under different storage conditions. The formulations were stable to sterilization by γ-irradiation and long term storage under freezing. The toxicity of the polymer and the formulations with gentamicin was examined by subcutaneous injection to rats. Four weeks after implantation, histopathological examination of the tissues surrounding the implant showed no inflammation. A preliminary study revealed positive effect of gentamicin containing P(SA-RA) on established osteomyelitis in a rat model. In conclusion this study suggests that poly(sebacic-co-ricinoleic-ester-anhydride) 3:7 loaded with 10%-20% gentamicin sulfate, might be used as an injectable biodegradable device for in situ treatment of osteomyelitis induced by S. aureus.
KW - Antibiotic
KW - Gentamicin
KW - Injectable polyner
KW - Osteomyelitis
KW - Staphylococcus aureus
KW - poly(ester-anhydride)
UR - http://www.scopus.com/inward/record.url?scp=33846573851&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2006.10.010
DO - 10.1016/j.jconrel.2006.10.010
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C2 - 17150275
AN - SCOPUS:33846573851
SN - 0168-3659
VL - 117
SP - 90
EP - 96
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -