A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss

Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilm formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortun...

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Autores principales:	Cong Yao, Meisong Zhu, Xiuguo Han, Qiang Xu, Min Dai, Tao Nie, Xuqiang Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	implant infection enoxacin aspartic acid octapeptide mesoporous silica nanoparticles bone-targeting Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/1050a6e1465c428ba58a8b04d50ff03c
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spelling	oai:doaj.org-article:1050a6e1465c428ba58a8b04d50ff03c2021-11-16T07:22:40ZA Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss2296-418510.3389/fbioe.2021.749910https://doaj.org/article/1050a6e1465c428ba58a8b04d50ff03c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.749910/fullhttps://doaj.org/toc/2296-4185Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilm formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortunately, enoxacin exerts both antibacterial and osteoclast inhibitory effects, playing a role in limiting infection and preventing bone loss. However, enoxacin lacks specificity in bone tissue and low bioavailability-related adverse effects, which hinders translational practice. Here, we developed a nanosystem (Eno@MSN-D) based on enoxacin (Eno)-loaded mesoporous silica nanoparticles (MSN), decorated with the eight repeating sequences of aspartate (D-Asp8), and coated with polyethylene glycol The release results suggested that Eno@MSN-D exhibits a high sensitivity to acidic environment. Moreover, this Eno@MSN-D delivery nanosystem exhibited both antibacterial and anti-osteoclast properties in vitro. The cytotoxicity assay revealed no cytotoxicity at the low concentration (20 μg/ml) and Eno@MSN-D inhibited RANKL-induced osteoclast differentiation. Importantly, Eno@MSN-D allowed the targeted release of enoxacin in infected bone tissue. Bone morphometric analysis and histopathology assays demonstrated that Eno@MSN-D has antibacterial and antiosteoclastic effects in vivo, thereby preventing implant-related infections and bone loss. Overall, our study highlights the significance of novel biomaterials that offer new alternatives to treat and prevent orthopaedic Staphylococcus aureus-related implantation infections and bone loss.Cong YaoMeisong ZhuXiuguo HanQiang XuMin DaiTao NieXuqiang LiuFrontiers Media S.A.articleimplant infectionenoxacinaspartic acid octapeptidemesoporous silica nanoparticlesbone-targetingBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	implant infection enoxacin aspartic acid octapeptide mesoporous silica nanoparticles bone-targeting Biotechnology TP248.13-248.65
spellingShingle	implant infection enoxacin aspartic acid octapeptide mesoporous silica nanoparticles bone-targeting Biotechnology TP248.13-248.65 Cong Yao Meisong Zhu Xiuguo Han Qiang Xu Min Dai Tao Nie Xuqiang Liu A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss
description	Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilm formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortunately, enoxacin exerts both antibacterial and osteoclast inhibitory effects, playing a role in limiting infection and preventing bone loss. However, enoxacin lacks specificity in bone tissue and low bioavailability-related adverse effects, which hinders translational practice. Here, we developed a nanosystem (Eno@MSN-D) based on enoxacin (Eno)-loaded mesoporous silica nanoparticles (MSN), decorated with the eight repeating sequences of aspartate (D-Asp8), and coated with polyethylene glycol The release results suggested that Eno@MSN-D exhibits a high sensitivity to acidic environment. Moreover, this Eno@MSN-D delivery nanosystem exhibited both antibacterial and anti-osteoclast properties in vitro. The cytotoxicity assay revealed no cytotoxicity at the low concentration (20 μg/ml) and Eno@MSN-D inhibited RANKL-induced osteoclast differentiation. Importantly, Eno@MSN-D allowed the targeted release of enoxacin in infected bone tissue. Bone morphometric analysis and histopathology assays demonstrated that Eno@MSN-D has antibacterial and antiosteoclastic effects in vivo, thereby preventing implant-related infections and bone loss. Overall, our study highlights the significance of novel biomaterials that offer new alternatives to treat and prevent orthopaedic Staphylococcus aureus-related implantation infections and bone loss.
format	article
author	Cong Yao Meisong Zhu Xiuguo Han Qiang Xu Min Dai Tao Nie Xuqiang Liu
author_facet	Cong Yao Meisong Zhu Xiuguo Han Qiang Xu Min Dai Tao Nie Xuqiang Liu
author_sort	Cong Yao
title	A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss
title_short	A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss
title_full	A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss
title_fullStr	A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss
title_full_unstemmed	A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss
title_sort	bone-targeting enoxacin delivery system to eradicate staphylococcus aureus-related implantation infections and bone loss
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1050a6e1465c428ba58a8b04d50ff03c
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A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss

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