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ENHANCED GENTAMICIN RELEASE FROM ANTIBIOTIC-LOADED ACRYLIC BEADS UNDER THE INFLUENCE OF ULTRASOUNDS



Abstract

Introduction: Local drug delivery yields higher gentamicin concentrations than can be safely achieved with systemic application. Unfortunately, both for beads as well as for bone cements, a sharp drop in release follows high initial gentamicin release. Aim of this study is to compare the effects of pulsed ultrasound on the release of gentamicin from antibiotic-loaded beads and bone cements. Mercury intrusion porosimetry is carried out to compare the pore size distribution in both materials before and after antibiotic release.

Materials and Methods: Ultrasound: Gentamicin release from three brands of gentamicin-loaded bone cement (CMW 1, Palamed G and Palacos R-G) and Septopal gentamicin-loaded beads was measured after 18 h of exposure in PBS to an ultrasonic field of 46.5 kHz in a 1:3 duty cycle with a peak intensity of 500 mW/cm2 at the sample position. Ultrasound experiments were performed for 18h in 9-fold on bone cement and in 6-fold on beads. Samples not exposed to ultrasound were used as controls. The gentamicin release was measured with fluorescence polarisation immunoassay. Gentamicin release from insonated and control groups was compared using a two-tailed Student’s t test for independent samples.

Mercury intrusion porosimetry: In order to mimic bone cement and beads after prolonged stay in the human body (i.e. after initial release of the loaded gentamicin) samples were immersed for four and two weeks, in PBS. Immersed and not-immersed samples were compared.

Results: Pulsed ultrasound significantly enhanced gentamicin release from gentamicin-loaded beads, whereas gentamicin release from the gentamicin-loaded bone cements was not significantly enhanced. Mercury intrusion porosimetry revealed a rise in pores between 0.1 and 0.01 um in beads after gentamicin release, while in bone cements no increase in the number of pores before and after antibiotic release was found.

Conclusions: Ultrasound increases gentamicin release from antibiotic-loaded acrylic beads by 15%. Development of pores coincides with increased gentamicin release by ultrasound for beads. Application of ultrasound could optimise usage of an (antibiotic) reservoir in local drug delivery systems to treat bone and soft tissue infections more effectively.

The abstracts were prepared by editorial secretary, Mrs K. Papastefanou. Correspondence should be addressed to Professor K.N. Malizos, Department of Orthopaedic Surgery, School of Medicine, University of Thessalia, Larissa, 41222 GREECE