Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis

Melissa C Rivera,1 Stefano Perni,1 Alastair Sloan,2 Polina Prokopovich1 1School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK; 2School of Dentistry, Cardiff University, Heath Park, Cardiff, Wales, UK Background: Aseptic loosening, as a consequence of an extended inflamma...

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Autores principales:	Rivera MC, Perni S, Sloan A, Prokopovich P
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Titanium Dexamethasone Macrophages Aseptic loosening TJR implant Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/25b74674adf148118c7c15cc2b71a6be
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spelling	oai:doaj.org-article:25b74674adf148118c7c15cc2b71a6be2021-12-02T02:21:41ZAnti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis1178-2013https://doaj.org/article/25b74674adf148118c7c15cc2b71a6be2019-02-01T00:00:00Zhttps://www.dovepress.com/anti-inflammatory-drug-eluting-implant-model-system-to-prevent-wear-pa-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Melissa C Rivera,1 Stefano Perni,1 Alastair Sloan,2 Polina Prokopovich1 1School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK; 2School of Dentistry, Cardiff University, Heath Park, Cardiff, Wales, UK Background: Aseptic 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. Methods: In 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. Results: Zeta 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-α 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. Conclusion: Dexamethasone released from amino functionalized titanium can offer the possibility of preventing asepting loosening of joint replacement devices. Keywords: titanium, dexamethasone, macrophages, aseptic loosening, TJR, implantRivera MCPerni SSloan AProkopovich PDove Medical PressarticleTitaniumDexamethasoneMacrophagesAseptic looseningTJRimplantMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1069-1084 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Titanium Dexamethasone Macrophages Aseptic loosening TJR implant Medicine (General) R5-920
spellingShingle	Titanium Dexamethasone Macrophages Aseptic loosening TJR implant Medicine (General) R5-920 Rivera MC Perni S Sloan A Prokopovich P Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis
description	Melissa C Rivera,1 Stefano Perni,1 Alastair Sloan,2 Polina Prokopovich1 1School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK; 2School of Dentistry, Cardiff University, Heath Park, Cardiff, Wales, UK Background: Aseptic 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. Methods: In 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. Results: Zeta 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-α 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. Conclusion: Dexamethasone released from amino functionalized titanium can offer the possibility of preventing asepting loosening of joint replacement devices. Keywords: titanium, dexamethasone, macrophages, aseptic loosening, TJR, implant
format	article
author	Rivera MC Perni S Sloan A Prokopovich P
author_facet	Rivera MC Perni S Sloan A Prokopovich P
author_sort	Rivera MC
title	Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis
title_short	Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis
title_full	Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis
title_fullStr	Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis
title_full_unstemmed	Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis
title_sort	anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/25b74674adf148118c7c15cc2b71a6be
work_keys_str_mv	AT riveramc antiinflammatorydrugelutingimplantmodelsystemtopreventwearparticleinducedperiprostheticosteolysis AT pernis antiinflammatorydrugelutingimplantmodelsystemtopreventwearparticleinducedperiprostheticosteolysis AT sloana antiinflammatorydrugelutingimplantmodelsystemtopreventwearparticleinducedperiprostheticosteolysis AT prokopovichp antiinflammatorydrugelutingimplantmodelsystemtopreventwearparticleinducedperiprostheticosteolysis
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Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis

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