Drug release from bone implants in vitro - Simbone

Introduction

Fig. 1 - Orthopaedic implant model

Orthopaedic implants are widely used as drug carriers for local drug delivery to minimize the risk of infection for the patients post surgery. Ideally, the drug release kinetics of these implants should be assessed in vivo through animal or human trials. However this can be expensive and time-consuming. In-vitro-testing is a more affordable and simpler alternative. Conventional in-vitro-methods are mostly too simplistic (e.g. paddle apparatus). They disregard the complexities of in-vivo-situations and do not allow a valid in-vitro/in-vivo-correlation. This work proposes a new in-vitro-method that takes into account drug diffusion and transport at the bone-implant-interface by use of a hydrogel membrane and a flow cell.

Methods

The model comprises of a compartment containing the test sample (e.g. coated implant sample or test drug solution) that is separated from a flow channel by a hydrogel membrane. The flow channel is connected in series with a peristaltic pump and a fluorescence flow-through cuvette in a closed-loop configuration. The first set of measurements uses a 1 mM fluorescein sodium aqueous solution as the test drug. The dye diffuses through the hydrogel membrane into the flow channel and concentration is monitored continuously by fluorescence spectroscopy.

Results and Conclusion

Fig. 2 - Flow cell
Fig. 3 - Fluorescence measurement

Test drug concentration in the main flow circuit reaches a saturation value after one week. The thickness of the hydrogel membrane strongly influences the drug release rate.

The proposed method can be used for continuous monitoring of the drug release process. Drug diffusion and transport rates can be varied by changing the thickness of the hydrogel membrane and the flow in the circuit. Future measurements will be carried out with coated implant models. Parameters like membrane thickness and flow rate should be tuned to match in vivo data reported in the literature.