A new method of drug delivery using degradable magnesium orthopaedic implants: a proof of concept

摘要

Introduction: Resorbable, non-permanent implants are advantageous over permanent implants in appropriate applications such as cardiovascular stents and orthopaedic fixation devices. Bone fractures often require fixation devices, such as screws, nails, rods, wires and plates, to immobilize the bone during healing and are not required to remain after the bone is rehabilitated. Non-permanent implants dissolve safely in the body and no surgery is required for implant retrieval, reducing the cost and complications associated with additional surgery. The ability of magnesium to safely degrade can be potentially utilised to release drugs as the implant degrades. This system would allow for the controlled release of drugs directly to the implant site; resulting in lower doses and reduced side effects. Magnesium is the stand out material for non-permanent implants and has received increasing attention in the literature. Magnesium degrades in the body and excess magnesium is harmlessly excreted via the kidneys. Magnesium has similar mechanical properties to bone as compared with traditional permanent fixation device materials such as stainless steel and titanium. Degradation rate of magnesium alloys can be tailored by alloying with other elements. To the best of our knowledge there are currently no studies investigating the local delivery of pharmaceutical agents from magnesium biodegradable orthopaedic implants. This study aims to prove this concept through in vitro investigation. Materials and Methods: High purity magnesium (99.99%) samples for in vitro testing were 20 mm, 5 mm in width and 5 mm height, with 9 reservoirs of 1 mm in diameter placed every 2 mm. The reservoirs were filled with a model drug, ibuprofen sodium salt, and encased in epoxy to mimic an orthopaedic screw in bone. One face of the sample was exposed by polishing to 1200 grit SiC paper with ethanol in order to encourage degradation down the length of the sample. Immersion testing, to determine the rate of degradation, was carried out for 28 days in a CO2 incubator at 37°C in 200 mL of minimum Essential Media with a sodium bicarbonate (2.2 g/L) buffer. The solution was replenished every 2-3 days to maintain salt levels. Aliquots were taken every 2-3 days. Ibuprofen was detected in solution using Ultraviolet Visible spectroscopy. The magnesium samples were imaged and analysed using an optical microscopy and a Scanning Electron Microscope with an Oxford Instruments X-Max 80 EDS detector. Results and Discussion: Magnesium was found to degrade in a predictable manner in vitro, degrading at a rate of 0.62 mm~2 per day. The surface of the magnesium showed no deep crevices or pits, indicating that dissolution was uniform duing immersion tests. The oxide film present on magnesium samples was found to contain a sublayer of magnesium and oxygen and a top porous layer rich in carbon and phosphorus as well as containing magnesium, oxygen, sodium and carbon. Ibuprofen was released in a linear manner and was detected using Uv-vis spectroscopy. Conclusion: This pilot study indicates the promise a degradable magnesium orthopaedic implants as drug delivery devices. An in vivo study using a rat animal model with a radiolabled model drug is currently in progress to validate the in vitro results.