In vitro/in vivo evaluation of the efficiency of teicoplanin-loaded biodegradable microparticles formulated for implantation to infected bone defects

Abstract

Chronic osteomyelitis is still the cause of many problems in orthopaedics in terms of therapy and infection persistence. Four-to-six week systemic antibiotic therapy is required along with bone and soft tissue debridement in the therapy of chronic osteomyelitis. Prolonged-release local antibiotic therapy has been taken into consideration due to the side effects encountered in long-term high dose antibiotic use and the duration of hospitalization of the patients. Although local antibiotic therapy has been achieved by bone cement, a second surgical operation is needed for the removal of the system. On the other hand, heat generation during cement curing limits the use of heat-sensitive active ingredients. The most frequent osteomyelitis inducing micro-organism is gram (+) Staphylococcus aureus. In this study, teicoplanin, a glycopeptide antibiotic, active on gram (+) bacteria, was incorporated in a synthetic polymer in order to prepare a microsphere formulation for implantation to bone defects. Particle size, surface characteristics, loading capacity and in vitro release characteristics of the microspheres were determined as well as stability assessment of teicoplanin under accelerated conditions. In vivo studies were performed on rabbits and the microparticles were implanted intra-articularly to the lateral condylus of the femur. Antibiotic presence was detected by a microbiological assay from synovial fluid sample aspirated throughout 5 weeks. In the light of these evaluations, microspheres prepared from PLGA (75:25) (Mw 136,000) polymer were determined to be effective, and promising for obtaining prolonged local antibiotic release.

Two-Stage Cementless Revision Total Hip Arthroplasty for Infected Primary Hip Arthroplasties

“…To date, there have been no prospectively designed, randomized, controlled trials comparing the antibiotic-impregnated cement spacer options with adequate numbers of patients and long-term follow-up to guide the clinical practice. In vivo/in vitro studies demonstrated that teicoplanin-impregnated cement spacers were found to be effective in the treatment of infected joint arthroplasties [30][31][32]. Teicoplanin covers only the Grampositive microorganisms and this may be considered as a disadvantage when used in antibiotic impregnated cement spacer during the first stage.…”

PLGA and PHBV Microsphere Formulations and Solid-State Characterization: Possible Implications for Local Delivery of Fusidic Acid for the Treatment and Prevention of Orthopaedic Infections

“…Due to the fundamental problems with PMMA, various biodegradable and bioresorbable carriers of antibiotics for the treatment and prevention of prosthetic joint infections have been studied based on poly (α-hydroxy acid) polymers such as PLGA (18)(19)(20) and PHBV (21)(22)(23). In particular, PLGA (19,20,(24)(25)(26) and PHBV (27,28) microspheres have been used to deliver a variety of antibiotics for the treatment of bone infections.…”

Antibiotic-loaded poly-ε-caprolactone and porous β-tricalcium phosphate composite for treating osteomyelitis

“…The biodegradable polymers that have been used include poly(D,L-lactic acid) [10,11], polylactide-co-glycolide [4,[12][13][14], copolymers of L-lactide and D,L-lactide [15], polyanhydrides of bis-carboxyphenoxypropane and sebacic acid [16], polycaprolactone [17][18][19], and polyhydroxyalkanoate [20]. These polymers release antibiotics for several hours to 40 weeks in vitro, and are effective for several weeks in vivo [21,22].…”