Antibiotic microspheres: preliminary testing for potential treatment of osteomyelitis.
Osteomyelitis is a difficult problem for orthopaedic surgeons. The current standard of treatment requires high doses of antibiotic to be administered parenterally, which can damage vital organs. A local drug delivery system, which targets only the infected tissues, would eliminate some of the complications associated with extended courses of parenteral antibiotic treatment. In the current study, biodegradable microspheres were manufactured from a high molecular weight copolymer of 50% lactic and 50% glycolic acid and the antibiotic tobramycin. Various formulations of microspheres were tested for in vitro elution characteristics to determine the optimum formulation for linear release of antibiotic for at least 4 weeks. The optimal formulation then was implanted into a pouch created in the quadriceps muscle of mice to evaluate the in vivo elution of the antibiotic and the inflammatory response elicited by the microspheres. Results indicate that a sustained linear release of antibiotic from the microspheres is possible for a period of at least 4 weeks and that the inflammatory response was within levels required for the microspheres to be considered biocompatible.
Ambrose
Catherine G
CG
Department of Orthopaedics, University of Texas Health Science Center at Houston, Houston, TX, USA.
Gogola
Gloria R
GR
Clyburn
Terry A
TA
Raymond
A Kevin
AK
Peng
Angela S
AS
Mikos
Antonios G
AG
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D001672:Biocompatible Materials / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D007249:Inflammation / Q000139:chemically induced; D051379:Mice; D008813:Mice, Inbred ICR; D008863:Microspheres; D008970:Molecular Weight; D018482:Muscle, Skeletal / Q000187:drug effects; D010019:Osteomyelitis / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D011098:Polyglactin 910 / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D014031:Tobramycin / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D014031:Tobramycin