Influence of lactose addition to gentamicin-loaded acrylic bone cement on the kinetics of release of the antibiotic and the cement properties.

The purpose of this study was to characterize a poly(methyl methacrylate) bone cement that was loaded with the antibiotic gentamicin sulphate (GS) and lactose, which served to modulate the release of GS from cement specimens. The release of GS when the cement specimens were immersed in phosphate-buffered saline at 37 degrees Celsius was determined spectrophotometrically. The microstructure, porosity, density, tensile properties and flexural properties of the cements were determined before and after release of GS. A kinetics model of the release of GS from the cement that involved a coupled mechanism based on dissolution/diffusion processes and an initial burst effect was proposed. Dissolution assay results showed that drug elution was controlled by a diffusion mechanism which can be modulated by lactose addition. Density values and mechanical properties (tensile strength, flexural strength, elastic modulus and fracture toughness) were reduced by the increased porosity resulting from lactose addition, but maintained acceptable values for the structural functions of bone cement. The present results suggest that lactose-modified, gentamicin-loaded acrylic bone cements are potential candidates for use in various orthopaedic and dental applications.

Improvement of gentamicin poly(D,L-lactic-co-glycolic acid) microspheres for treatment of osteomyelitis induced by orthopedic procedures.

Poly(D,L-lactide-co-glycolide) (PLGA) biodegradable microspheres with gentamicin for local treatment of microbial bone infection were prepared and characterized. Gentamicin was assayed spectrophotometrically at 332 nm after derivation with the o-phthalaldehyde; biodegradable polymers studied did not interfere with this method of gentamicin analysis. PLGA microspheres were made by the double emulsion solvent evaporation method with modifications. The first W(1)/O emulsion was obtained by ultrasonication or high-speed homogenization, and a large aqueous phase W(2) (200 ml) was used. The ultrasonication method increases the microsphere percentage observed in the 20-40 microm size range and, in all cases SEM-microphotographs revealed homogeneous and spherically shaped particles with smooth surfaces. The method including ultrasonication proposed in the present work improved the encapsulation efficiency of gentamicin by nearly 100% (97.94%). Several mathematical models based on heterogeneous hydrolytic degradation were applied to evaluate their suitability in describing gentamicin released from PLGA microspheres. Two models, one of them including an autocatalytic process, were finally proposed to contribute to understand the mass transport mechanism involved in drug release from these microspheres.