Key-properties outlook of a levofloxacin-loaded acrylic bone cement with improved antibiotic delivery
[Display omitted] •Novel lactose-modified acrylic bone cement with improved antibiotic (levofloxacin) release.•7-week release of levofloxacin with antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli.•Improved inhibition of Staphylococcus aureus biofi...
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Veröffentlicht in: | International journal of pharmaceutics 2015-05, Vol.485 (1-2), p.317-328 |
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creator | Matos, Ana C. Ribeiro, Isabel A.C. Guedes, Rita C. Pinto, Rosana Vaz, Mário A. Gonçalves, Lídia M. Almeida, António J. Bettencourt, Ana F. |
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•Novel lactose-modified acrylic bone cement with improved antibiotic (levofloxacin) release.•7-week release of levofloxacin with antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli.•Improved inhibition of Staphylococcus aureus biofilm development by the lactose-modified bone cement matrix, when compared to the commercial acrylic bone cement matrix.•Maintenance of both mechanical integrity and biocompatibility of the modified acrylic bone cement.•Favorable covalent and non-covalent interactions between levofloxacin and the bone cement are evidenced by density functional calculations.
Antibiotic-loaded acrylic bone cements (ALABCs) are widely used to decrease the occurrence of bone infections in cemented arthroplasties and actually being considered as a more cost-effective procedure when compared to cementless implants. However, ALABCs have a major drawback, which is the incomplete release of the antibiotics and, as a result, pathogens that commonly are responsible for those infections are becoming resistant. Consequently, it is of most relevance to find new antibacterial agents to load into BC with an effective mechanism against those microorganisms. This research work intended to load levofloxacin, a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues, on lactose-modified commercial bone cement (BC). This modified BC matrix exhibited increased levofloxacin release and delayed Staphylococcus aureus biofilm formation. Further insights on material-drug interaction during BC setting were investigated by density functional theory calculations. The obtained results suggested that favorable covalent and non-covalent interactions could be established between levofloxacin and the BC. Moreover, BC mechanical and biocompatibility properties were maintained. These features justify the potential of levofloxacin-loaded modified-BC as a valuable approach for local antibiotic delivery in bone infections management. |
doi_str_mv | 10.1016/j.ijpharm.2015.03.035 |
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•Novel lactose-modified acrylic bone cement with improved antibiotic (levofloxacin) release.•7-week release of levofloxacin with antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli.•Improved inhibition of Staphylococcus aureus biofilm development by the lactose-modified bone cement matrix, when compared to the commercial acrylic bone cement matrix.•Maintenance of both mechanical integrity and biocompatibility of the modified acrylic bone cement.•Favorable covalent and non-covalent interactions between levofloxacin and the bone cement are evidenced by density functional calculations.
Antibiotic-loaded acrylic bone cements (ALABCs) are widely used to decrease the occurrence of bone infections in cemented arthroplasties and actually being considered as a more cost-effective procedure when compared to cementless implants. However, ALABCs have a major drawback, which is the incomplete release of the antibiotics and, as a result, pathogens that commonly are responsible for those infections are becoming resistant. Consequently, it is of most relevance to find new antibacterial agents to load into BC with an effective mechanism against those microorganisms. This research work intended to load levofloxacin, a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues, on lactose-modified commercial bone cement (BC). This modified BC matrix exhibited increased levofloxacin release and delayed Staphylococcus aureus biofilm formation. Further insights on material-drug interaction during BC setting were investigated by density functional theory calculations. The obtained results suggested that favorable covalent and non-covalent interactions could be established between levofloxacin and the BC. Moreover, BC mechanical and biocompatibility properties were maintained. These features justify the potential of levofloxacin-loaded modified-BC as a valuable approach for local antibiotic delivery in bone infections management.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2015.03.035</identifier><identifier>PMID: 25797053</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Biofilms - drug effects ; Biofilms - growth & development ; Cell Line ; Chemistry, Pharmaceutical ; Computer Simulation ; Controlled release ; Delayed-Action Preparations ; Density functional theory ; Drug Carriers ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Fluoroquinolone ; Kinetics ; Lactose - chemistry ; Levofloxacin - administration & dosage ; Levofloxacin - chemistry ; Levofloxacin - pharmacology ; Mice ; Microscopy, Electron, Scanning ; Models, Chemical ; Models, Molecular ; Molecular Structure ; Osteoblasts - drug effects ; Osteoblasts - metabolism ; Poly(methylmethacrylate) ; Polymethyl Methacrylate - administration & dosage ; Polymethyl Methacrylate - chemistry ; Polymethyl Methacrylate - pharmacology ; Solubility ; Staphylococcus aureus - drug effects ; Staphylococcus aureus - growth & development ; Staphylococcus-infection ; Surface Properties ; Technology, Pharmaceutical - methods</subject><ispartof>International journal of pharmaceutics, 2015-05, Vol.485 (1-2), p.317-328</ispartof><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-1eb4b849023732d414c8cf614f002def6f90802f13aaf4c6362ad76447402a3d3</citedby><cites>FETCH-LOGICAL-c412t-1eb4b849023732d414c8cf614f002def6f90802f13aaf4c6362ad76447402a3d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijpharm.2015.03.035$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25797053$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matos, Ana C.</creatorcontrib><creatorcontrib>Ribeiro, Isabel A.C.</creatorcontrib><creatorcontrib>Guedes, Rita C.</creatorcontrib><creatorcontrib>Pinto, Rosana</creatorcontrib><creatorcontrib>Vaz, Mário A.</creatorcontrib><creatorcontrib>Gonçalves, Lídia M.</creatorcontrib><creatorcontrib>Almeida, António J.</creatorcontrib><creatorcontrib>Bettencourt, Ana F.</creatorcontrib><title>Key-properties outlook of a levofloxacin-loaded acrylic bone cement with improved antibiotic delivery</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
•Novel lactose-modified acrylic bone cement with improved antibiotic (levofloxacin) release.•7-week release of levofloxacin with antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli.•Improved inhibition of Staphylococcus aureus biofilm development by the lactose-modified bone cement matrix, when compared to the commercial acrylic bone cement matrix.•Maintenance of both mechanical integrity and biocompatibility of the modified acrylic bone cement.•Favorable covalent and non-covalent interactions between levofloxacin and the bone cement are evidenced by density functional calculations.
Antibiotic-loaded acrylic bone cements (ALABCs) are widely used to decrease the occurrence of bone infections in cemented arthroplasties and actually being considered as a more cost-effective procedure when compared to cementless implants. However, ALABCs have a major drawback, which is the incomplete release of the antibiotics and, as a result, pathogens that commonly are responsible for those infections are becoming resistant. Consequently, it is of most relevance to find new antibacterial agents to load into BC with an effective mechanism against those microorganisms. This research work intended to load levofloxacin, a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues, on lactose-modified commercial bone cement (BC). This modified BC matrix exhibited increased levofloxacin release and delayed Staphylococcus aureus biofilm formation. Further insights on material-drug interaction during BC setting were investigated by density functional theory calculations. The obtained results suggested that favorable covalent and non-covalent interactions could be established between levofloxacin and the BC. Moreover, BC mechanical and biocompatibility properties were maintained. These features justify the potential of levofloxacin-loaded modified-BC as a valuable approach for local antibiotic delivery in bone infections management.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Biofilms - drug effects</subject><subject>Biofilms - growth & development</subject><subject>Cell Line</subject><subject>Chemistry, Pharmaceutical</subject><subject>Computer Simulation</subject><subject>Controlled release</subject><subject>Delayed-Action Preparations</subject><subject>Density functional theory</subject><subject>Drug Carriers</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Fluoroquinolone</subject><subject>Kinetics</subject><subject>Lactose - chemistry</subject><subject>Levofloxacin - administration & dosage</subject><subject>Levofloxacin - chemistry</subject><subject>Levofloxacin - pharmacology</subject><subject>Mice</subject><subject>Microscopy, Electron, Scanning</subject><subject>Models, Chemical</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - metabolism</subject><subject>Poly(methylmethacrylate)</subject><subject>Polymethyl Methacrylate - administration & dosage</subject><subject>Polymethyl Methacrylate - chemistry</subject><subject>Polymethyl Methacrylate - pharmacology</subject><subject>Solubility</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Staphylococcus aureus - growth & development</subject><subject>Staphylococcus-infection</subject><subject>Surface Properties</subject><subject>Technology, Pharmaceutical - methods</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEuPEzEQhC3Eig0LPwHkI5cJ7cfYkxNCK15ipb0sZ8tjt7UOnnGwnbD590yUwBWppb58VdVdhLxhsGbA1PvtOm53j7ZMaw6sX4NYpn9GVmzQohNSq-dkBUIPXc-0uCYva90CgOJMvCDXvNcbDb1YEfyOx25X8g5Li1hp3reU80-aA7U04SGHlJ-si3OXsvXoqXXlmKKjY56ROpxwbvR3bI80TovN4UTMLY4xtwXymOIBy_EVuQo2VXx92Tfkx-dPD7dfu7v7L99uP951TjLeOoajHAe5AS604F4y6QYXFJMBgHsMKmxgAB6YsDZIp4Ti1mslpZbArfDihrw7-y6n_NpjbWaK1WFKdsa8r4YpzRWDjeIL2p9RV3KtBYPZlTjZcjQMzKlhszWXhs2pYQNimX7Rvb1E7McJ_T_V30oX4MMZwOXRQ8Riqos4O_SxoGvG5_ifiD8Q5ZCK</recordid><startdate>20150515</startdate><enddate>20150515</enddate><creator>Matos, Ana C.</creator><creator>Ribeiro, Isabel A.C.</creator><creator>Guedes, Rita C.</creator><creator>Pinto, Rosana</creator><creator>Vaz, Mário A.</creator><creator>Gonçalves, Lídia M.</creator><creator>Almeida, António J.</creator><creator>Bettencourt, Ana F.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150515</creationdate><title>Key-properties outlook of a levofloxacin-loaded acrylic bone cement with improved antibiotic delivery</title><author>Matos, Ana C. ; Ribeiro, Isabel A.C. ; Guedes, Rita C. ; Pinto, Rosana ; Vaz, Mário A. ; Gonçalves, Lídia M. ; Almeida, António J. ; Bettencourt, Ana F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-1eb4b849023732d414c8cf614f002def6f90802f13aaf4c6362ad76447402a3d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Biofilms - drug effects</topic><topic>Biofilms - growth & development</topic><topic>Cell Line</topic><topic>Chemistry, Pharmaceutical</topic><topic>Computer Simulation</topic><topic>Controlled release</topic><topic>Delayed-Action Preparations</topic><topic>Density functional theory</topic><topic>Drug Carriers</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Fluoroquinolone</topic><topic>Kinetics</topic><topic>Lactose - chemistry</topic><topic>Levofloxacin - administration & dosage</topic><topic>Levofloxacin - chemistry</topic><topic>Levofloxacin - pharmacology</topic><topic>Mice</topic><topic>Microscopy, Electron, Scanning</topic><topic>Models, Chemical</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - metabolism</topic><topic>Poly(methylmethacrylate)</topic><topic>Polymethyl Methacrylate - administration & dosage</topic><topic>Polymethyl Methacrylate - chemistry</topic><topic>Polymethyl Methacrylate - pharmacology</topic><topic>Solubility</topic><topic>Staphylococcus aureus - drug effects</topic><topic>Staphylococcus aureus - growth & development</topic><topic>Staphylococcus-infection</topic><topic>Surface Properties</topic><topic>Technology, Pharmaceutical - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matos, Ana C.</creatorcontrib><creatorcontrib>Ribeiro, Isabel A.C.</creatorcontrib><creatorcontrib>Guedes, Rita C.</creatorcontrib><creatorcontrib>Pinto, Rosana</creatorcontrib><creatorcontrib>Vaz, Mário A.</creatorcontrib><creatorcontrib>Gonçalves, Lídia M.</creatorcontrib><creatorcontrib>Almeida, António J.</creatorcontrib><creatorcontrib>Bettencourt, Ana F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matos, Ana C.</au><au>Ribeiro, Isabel A.C.</au><au>Guedes, Rita C.</au><au>Pinto, Rosana</au><au>Vaz, Mário A.</au><au>Gonçalves, Lídia M.</au><au>Almeida, António J.</au><au>Bettencourt, Ana F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Key-properties outlook of a levofloxacin-loaded acrylic bone cement with improved antibiotic delivery</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2015-05-15</date><risdate>2015</risdate><volume>485</volume><issue>1-2</issue><spage>317</spage><epage>328</epage><pages>317-328</pages><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
•Novel lactose-modified acrylic bone cement with improved antibiotic (levofloxacin) release.•7-week release of levofloxacin with antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli.•Improved inhibition of Staphylococcus aureus biofilm development by the lactose-modified bone cement matrix, when compared to the commercial acrylic bone cement matrix.•Maintenance of both mechanical integrity and biocompatibility of the modified acrylic bone cement.•Favorable covalent and non-covalent interactions between levofloxacin and the bone cement are evidenced by density functional calculations.
Antibiotic-loaded acrylic bone cements (ALABCs) are widely used to decrease the occurrence of bone infections in cemented arthroplasties and actually being considered as a more cost-effective procedure when compared to cementless implants. However, ALABCs have a major drawback, which is the incomplete release of the antibiotics and, as a result, pathogens that commonly are responsible for those infections are becoming resistant. Consequently, it is of most relevance to find new antibacterial agents to load into BC with an effective mechanism against those microorganisms. This research work intended to load levofloxacin, a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues, on lactose-modified commercial bone cement (BC). This modified BC matrix exhibited increased levofloxacin release and delayed Staphylococcus aureus biofilm formation. Further insights on material-drug interaction during BC setting were investigated by density functional theory calculations. The obtained results suggested that favorable covalent and non-covalent interactions could be established between levofloxacin and the BC. Moreover, BC mechanical and biocompatibility properties were maintained. These features justify the potential of levofloxacin-loaded modified-BC as a valuable approach for local antibiotic delivery in bone infections management.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25797053</pmid><doi>10.1016/j.ijpharm.2015.03.035</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Biofilms - drug effects Biofilms - growth & development Cell Line Chemistry, Pharmaceutical Computer Simulation Controlled release Delayed-Action Preparations Density functional theory Drug Carriers Fibroblasts - drug effects Fibroblasts - metabolism Fluoroquinolone Kinetics Lactose - chemistry Levofloxacin - administration & dosage Levofloxacin - chemistry Levofloxacin - pharmacology Mice Microscopy, Electron, Scanning Models, Chemical Models, Molecular Molecular Structure Osteoblasts - drug effects Osteoblasts - metabolism Poly(methylmethacrylate) Polymethyl Methacrylate - administration & dosage Polymethyl Methacrylate - chemistry Polymethyl Methacrylate - pharmacology Solubility Staphylococcus aureus - drug effects Staphylococcus aureus - growth & development Staphylococcus-infection Surface Properties Technology, Pharmaceutical - methods |
title | Key-properties outlook of a levofloxacin-loaded acrylic bone cement with improved antibiotic delivery |
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