<p>Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis</p>

Abstract

BackgroundAseptic loosening, as a consequence of an extended inflammatory reaction induced by wear particles, has been classified as one of the most common complications of total joint replacement (TJR). Despite its high incidence, no therapeutical approach has yet been found to prevent aseptic loosening, leaving revision as only effective treatment. The local delivery of anti-inflammatory drugs to modulate wear-induced inflammation has been regarded as a potential therapeutical approach to prevent aseptic-loosening.MethodsIn this context, we developed and characterized anti-inflammatory drug-eluting TiO2 surfaces, using nanoparticles as a model for larger surfaces. The eluting surfaces were obtained by conjugating dexamethasone to carboxyl-functionalized TiO2 particles, obtained by using either silane agents with amino or mercapto moieties.ResultsZeta potential measurements, thermogravimetric analysis (TGA) and drug release results suggest that dexamethasone was successfully loaded onto the TiO2 particles. Release was pH dependent and greater amounts of drug were observed from amino route functionalized surfaces. The model-system was then tested for its cytotoxic and anti-inflammatory properties in LPS-stimulated macrophages. Dexamethasone released from amino route functionalized surfaces TiO2 particles was able to decrease LPS-induced nitric oxide (NO) and TNF-a production similarly to pure DEX at the same concentration; DEX released from mercapto route functionalized surfaces was at a too low concentration to be effective.ConclusionDexamethasone released from amino functionalized titanium can offer the possibility of preventing asepting loosening of joint replacement devices.

Particle release from implantoplasty of dental implants and impact on cells

“…The use of metallic dental implants has relatively high reliability and long-term success rates; however, it is not without complications and the need for ongoing maintenance persists. Particles are generated during the life span of an implant, and this can have significant physiological implications such as disrupted osseointegration and bone resorption (osteolysis) that may in turn lead to implant loss [ 3 , 4 ]. Particles can be released during implant bed preparation, from implant surface due to shear forces during fixture insertion, from implant-abutment interface due to wear and during functional loading [ 5 , 6 ].…”

Amplify antimicrobial photo dynamic therapy efficacy with poly-beta-amino esters (PBAEs)

“…PBAE were first described as gene transfer vectors 32 ; subsequent evidence has validated such properties and identified key features and optimised the polymer chain backbone in order to maximise the opportunities offered by such polymers to transfer genes into target cells 35 , 51 . Further applications of PBAEs have been proposed for cancer drug delivery 52 – 55 , in layer-by-layer deposition of drug releasing coatings 41 , 56 – 61 and drug localisation in cartilage 33 , 34 ; currently no application of these polymers in antimicrobial technologies has been reported. Depending on the application, different PBAE features have been shown to pivot the outcome; for example PBAEs belonging to the family of B3 and A16 are known cell uptake enhancer in DNA delivery 32 , 35 , 51 while A5 and B5 are better at driving drug uptake into cartilage 34 ; additionally it has also been proven that end-capping has a further critical role 34 , 35 .…”

“…Total and released LDH (indicated as LDH total and LDH released respectively) were determined as OD, at 490 nm, after correcting for the reading from the negative control. Cell viability was calculated according to the following equation: 41 …”

<p>Nanoparticle-based model of anti-inflammatory drug releasing LbL coatings for uncemented prosthesis aseptic loosening prevention</p>

“…Titanium oxide nanoparticles were functionalized with amino groups (Ti-O-NH 2 ) via silanation in toluene. Briefly, the particles were dispersed in toluene containing APTS for 24 hrs followed by repeated centrifugation/washing 25…”

“…The deposition of antibiotics on surfaces using LbL enabled prolonged release of these drugs 23,24. Controlled release of DEX from titanium surfaces has not been satisfactorily achieved as the direct conjugation did not sustain release for more than a few days 25. In this work, such steroidal drug was embedded into a dissolvable coating made using alginate and a polymer belonging to the class of poly-beta-amino-esters (PBAEs) 26.…”