Multifunctional implant coatings providing possibilities for fast antibiotics loading with subsequent slow release

Abstract

The possibility to fast-load biomimetic hydroxyapatite coatings on surgical implant with the antibiotics Amoxicillin, Gentamicin sulfate, Tobramycin and Cephalothin has been investigated in order to develop a multifunctional implant device offering sustained local anti-bacterial treatment and giving the surgeon the possibility to choose which antibiotics to incorporate in the implant at the site of surgery. Physical vapor deposition was used to coat titanium surfaces with an adhesion enhancing gradient layer of titanium oxide having an amorphous oxygen poor composition at the interface and a crystalline bioactive anatase TiO(2) composition at the surface. Hydroxyapatite (HA) was biomimetically grown on the bioactive TiO(2) to serve as a combined bone in-growth promoter and drug delivery vehicle. The coating was characterized using scanning and transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The antibiotics were loaded into the HA coatings via soaking and the subsequent release and antibacterial effect were analyzed using UV spectroscopy and examination of inhibition zones in a Staphylococcus aureus containing agar. It was found that a short drug loading time of 15 min ensured antibacterial effects after 24 h for all antibiotics under study. It was further found that the release processes of Cephalothin and Amoxicillin consisted of an initial rapid drug release that varied unpredictably in amount followed by a reproducible and sustained release process with a release rate independent of the drug loading times under study. Thus, implants that have been fast-loaded with drugs could be stored for ~10 min in a simulated body fluid after loading to ensure reproducibility in the subsequent release process. Calculated release rates and measurements of drug amounts remaining in the samples after 22 h of release indicated that a therapeutically relevant dose could be achieved close to the implant surface for about 2 days. Concluding, the present study provides an outline for the development of a fast-loading slow-release surgical implant kit where the implant and the drug are separated when delivered to the surgeon, thus constituting a flexible solution for the surgeon by offering the choice of quick addition of antibiotics to the implant coating based on the patient need.

Co-loading of bisphosphonates and antibiotics to a biomimetic hydroxyapatite coating

“…The incorporation of the two different molecules seems to be unaffected or even improved by the presence of the other. The release rate of cephalothin is in agreement with previous studies where it was sufficient for bacteria inhibition in the vicinity of the implant (Brohede et al 2009a). …”

“…BHA-coatings can carry antibiotics (Stigter et al 2004;Brohede et al 2009a) and bisphosphonates (Åberg et al 2009) individually but, to our knowledge, have these substances never been loaded simultaneously to a BHA-coating, which would promote a beneficial dual effect as described above. Thus, the present study was carried out to investigate the possibility to perform such a co-loading.…”

The biomimetic apatite-cefalotin coatings on modified titanium

“…However, it is necessary to ensure a sustained antibiotic release from the coated surface, because peri-implantitis is slow developing 5) . Also, a sustained antibiotic release may improve the safety of the dose and avoid side effects that can cause problems 16) .…”

“…Therefore, many studies have addressed this problem with limited success [7][8][9][10][11][12] . Therefore, to solve this problem, local drug delivery system through antibiotic coatings was developed [13][14][15][16][17] . Recently, precipitation coating method was introduced.…”

“…In this biomimetic precipitation method, the titanium implant is immersed into saturated solutions of calcium and phosphate that also contain antibiotics. When the calcium-phosphate crystals were precipitated, the antibiotics were coprecipitated [13][14][15][16] . Antibiotics that contain a carboxylic group, like cefalotin, have strong binding interactions with calcium.…”