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
Hauptverfasser: 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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container_end_page 328
container_issue 1-2
container_start_page 317
container_title International journal of pharmaceutics
container_volume 485
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.
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.
doi_str_mv 10.1016/j.ijpharm.2015.03.035
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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 &amp; dosage ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Biofilms - drug effects ; Biofilms - growth &amp; 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 &amp; 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 &amp; dosage ; Polymethyl Methacrylate - chemistry ; Polymethyl Methacrylate - pharmacology ; Solubility ; Staphylococcus aureus - drug effects ; Staphylococcus aureus - growth &amp; 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. 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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 &amp; dosage</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Biofilms - drug effects</subject><subject>Biofilms - growth &amp; 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 &amp; 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 &amp; 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 &amp; 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. ; 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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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ispartof International journal of pharmaceutics, 2015-05, Vol.485 (1-2), p.317-328
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source MEDLINE; Access via ScienceDirect (Elsevier)
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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