Bioerodible polyanhydrides for antibiotic drug delivery: in vivo osteomyelitis treatment in a rat model system.
Acute and chronic osteomyelitis can be difficult to treat by conventional means. Current methods of treatment involve the use of systemic antibiotics, the local implantation of non-degradable drug carriers, and surgical débridement. Each method has specific drawbacks. We report on the use of a new controlled release system utilizing gentamicin and bioerodible, biocompatible polymers (polyanhydrides) designed for drug delivery applications for the treatment of clinical osteomyelitis. We compared this system's ability to reduce bacterial levels in infected bone with that of conventional non-degradable delivery systems based on polymethylmethacrylate (PMMA) and gentamicin. Polyanhydride copolymers of bis-carboxyphenoxypropane and sebacic acid P loaded with gentamicin sulfate and PMMA/gentamicin matrices were implanted in the long bones of Sprague-Dawley rats infected with a strain of Staphylococcus aureus. After 3 weeks of implantation, the polymeric delivery devices were removed and quantitative cultures were used to determine bacterial levels in bone. The polyanhydride/gentamicin matrices demonstrated significant degradation over the 3 week implantation period. Levels of bacteria, measured in colony forming units, were significantly lower in bone implanted with the polyanhydride/gentamicin release system than in long bones of control animals without an implant (p < 0.01), of animals with a polyanhydride polymer implant alone (p < 0.01), and of animals with a PMMA/gentamicin implant (p = 0.03). Bioerodible polyanhydrides show promise as a new treatment modality for infections in bone.
Laurencin
C T
CT
Harvard-M.I.T. Division of Health Sciences and Technology, Cambridge, Massachusetts.
Gerhart
T
T
Witschger
P
P
Satcher
R
R
Domb
A
A
Rosenberg
A E
AE
Hanff
P
P
Edsberg
L
L
Hayes
W
W
Langer
R
R
D000818:Animals; D001672:Biocompatible Materials; D015169:Colony Count, Microbial; D003652:Decanoic Acids / Q000008:administration & dosage*; D003998:Dicarboxylic Acids; D004195:Disease Models, Animal; D005839:Gentamicins / Q000008:administration & dosage*; D062385:Hydroxybenzoates / Q000008:administration & dosage*; D008297:Male; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D011109:Polymethacrylic Acids / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000254:growth & development
D001672:Biocompatible Materials; D003652:Decanoic Acids; D003998:Dicarboxylic Acids; D005839:Gentamicins; D062385:Hydroxybenzoates; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; C011107:sebacic acid