Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent
Apatitic bone cements have been used as a clinical bone substitutes and drug delivery vehicles for therapeutic agents in orthopedic applications. This has led to their combination with different drugs with known ability to foster bone formation. Recent studies have evaluated Simvastatin for its role...
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| Veröffentlicht in: | Journal of biomedical materials research. Part B, Applied biomaterials Applied biomaterials, 2020-04, Vol.108 (3), p.760-770 |
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| container_title | Journal of biomedical materials research. Part B, Applied biomaterials |
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| creator | Khurana, Kanupriya Guillem‐Marti, Jordi Soldera, Flavio Mücklich, Frank Canal, Cristina Ginebra, Maria‐Pau |
| description | Apatitic bone cements have been used as a clinical bone substitutes and drug delivery vehicles for therapeutic agents in orthopedic applications. This has led to their combination with different drugs with known ability to foster bone formation. Recent studies have evaluated Simvastatin for its role in enhanced bone regeneration, but its lipophilicity hampers incorporation and release to and from the bone graft. In this study, injectable calcium phosphate foams (i‐CPF) based on α‐tricalcium phosphate were loaded for the first time with Pitavastatin. The stability of the drug in different conditions relevant to this study, the effect of the drug on the i‐CPFs properties, the release profile, and the in vitro biological performance with regard to mineralization and vascularization were investigated. Pitavastatin did not cause any changes in neither the micro nor the macro structure of the i‐CPFs, which retained their biomimetic features. PITA‐loaded i‐CPFs showed a dose‐dependent drug release, with early stage release kinetics clearly affected by the evolving microstructure due to the setting of cement. in vitro studies showed dose‐dependent enhancement of mineralization and vascularization. Our findings contribute towards the design of controlled release with low drug dosing bone grafts: i‐CPFs loaded with PITA as osteogenic and angiogenic agent. |
| doi_str_mv | 10.1002/jbm.b.34430 |
| format | Article |
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This has led to their combination with different drugs with known ability to foster bone formation. Recent studies have evaluated Simvastatin for its role in enhanced bone regeneration, but its lipophilicity hampers incorporation and release to and from the bone graft. In this study, injectable calcium phosphate foams (i‐CPF) based on α‐tricalcium phosphate were loaded for the first time with Pitavastatin. The stability of the drug in different conditions relevant to this study, the effect of the drug on the i‐CPFs properties, the release profile, and the in vitro biological performance with regard to mineralization and vascularization were investigated. Pitavastatin did not cause any changes in neither the micro nor the macro structure of the i‐CPFs, which retained their biomimetic features. PITA‐loaded i‐CPFs showed a dose‐dependent drug release, with early stage release kinetics clearly affected by the evolving microstructure due to the setting of cement. in vitro studies showed dose‐dependent enhancement of mineralization and vascularization. Our findings contribute towards the design of controlled release with low drug dosing bone grafts: i‐CPFs loaded with PITA as osteogenic and angiogenic agent.</description><identifier>ISSN: 1552-4973</identifier><identifier>EISSN: 1552-4981</identifier><identifier>DOI: 10.1002/jbm.b.34430</identifier><identifier>PMID: 31187939</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Angiogenesis ; Biomedical materials ; Biomimetics ; Bone biomaterials ; Bone cements ; Bone grafts ; Bone growth ; Calcium ; Calcium phosphates ; Chemical compounds ; controlled drug release ; Controlled release ; Dosage ; Drug delivery ; Drug delivery systems ; Drug development ; Drug dosages ; endothelial progenitor cells ; Foams ; Grafting ; Immunosuppressive agents ; Lipophilicity ; Materials research ; Materials science ; Mesenchymal stem cells ; Mineralization ; Orthopedics ; Osteogenesis ; Pharmacology ; rat mesenchymal stem cells ; Regeneration ; Regeneration (physiology) ; Simvastatin ; Substitute bone ; Surgical implants ; Tricalcium phosphate ; Vascularization</subject><ispartof>Journal of biomedical materials research. 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Part B, Applied biomaterials</title><addtitle>J Biomed Mater Res B Appl Biomater</addtitle><description>Apatitic bone cements have been used as a clinical bone substitutes and drug delivery vehicles for therapeutic agents in orthopedic applications. This has led to their combination with different drugs with known ability to foster bone formation. Recent studies have evaluated Simvastatin for its role in enhanced bone regeneration, but its lipophilicity hampers incorporation and release to and from the bone graft. In this study, injectable calcium phosphate foams (i‐CPF) based on α‐tricalcium phosphate were loaded for the first time with Pitavastatin. The stability of the drug in different conditions relevant to this study, the effect of the drug on the i‐CPFs properties, the release profile, and the in vitro biological performance with regard to mineralization and vascularization were investigated. Pitavastatin did not cause any changes in neither the micro nor the macro structure of the i‐CPFs, which retained their biomimetic features. PITA‐loaded i‐CPFs showed a dose‐dependent drug release, with early stage release kinetics clearly affected by the evolving microstructure due to the setting of cement. in vitro studies showed dose‐dependent enhancement of mineralization and vascularization. Our findings contribute towards the design of controlled release with low drug dosing bone grafts: i‐CPFs loaded with PITA as osteogenic and angiogenic agent.</description><subject>Angiogenesis</subject><subject>Biomedical materials</subject><subject>Biomimetics</subject><subject>Bone biomaterials</subject><subject>Bone cements</subject><subject>Bone grafts</subject><subject>Bone growth</subject><subject>Calcium</subject><subject>Calcium phosphates</subject><subject>Chemical compounds</subject><subject>controlled drug release</subject><subject>Controlled release</subject><subject>Dosage</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Drug development</subject><subject>Drug dosages</subject><subject>endothelial progenitor cells</subject><subject>Foams</subject><subject>Grafting</subject><subject>Immunosuppressive agents</subject><subject>Lipophilicity</subject><subject>Materials research</subject><subject>Materials science</subject><subject>Mesenchymal stem cells</subject><subject>Mineralization</subject><subject>Orthopedics</subject><subject>Osteogenesis</subject><subject>Pharmacology</subject><subject>rat mesenchymal stem cells</subject><subject>Regeneration</subject><subject>Regeneration (physiology)</subject><subject>Simvastatin</subject><subject>Substitute bone</subject><subject>Surgical implants</subject><subject>Tricalcium phosphate</subject><subject>Vascularization</subject><issn>1552-4973</issn><issn>1552-4981</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kEtLAzEURoMoPqor9xJwI0hrJo95LFV8VCq60HXI445NmZnUSUbpvzdadeHCRfIlcDj38iF0mJFJRgg9W-h2oieMc0Y20G4mBB3zqsw2f98F20F7ISwSnBPBttEOy7KyqFi1i-pptwATlW4AG9UYN7R4OfdhOVcRcO1VG9Ld4zgHbKFxb9CvsK_xo4vqTYWoouuwCtiHCP4FOmew6mw6L-7nmyLuo61aNQEOvnOEnq-vni5vx7OHm-nl-WxsOONkrKkBa8u8sLxQnAoNtCpEpZgojLEiL6iheS6YqjXVmphSkVIzK0rLassJZyN0svYue_86QIiydcFA06gO_BAkTVMIp0VyjNDxH3Thh75L2yUqr0pGK5En6nRNmd6H0EMtl71rVb-SGZGf9ctUv9Tyq_5EH307B92C_WV_-k4AXQPvroHVfy55d3F_sbZ-AD65kKo</recordid><startdate>202004</startdate><enddate>202004</enddate><creator>Khurana, Kanupriya</creator><creator>Guillem‐Marti, Jordi</creator><creator>Soldera, Flavio</creator><creator>Mücklich, Frank</creator><creator>Canal, Cristina</creator><creator>Ginebra, Maria‐Pau</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>202004</creationdate><title>Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent</title><author>Khurana, Kanupriya ; Guillem‐Marti, Jordi ; Soldera, Flavio ; Mücklich, Frank ; Canal, Cristina ; Ginebra, Maria‐Pau</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4340-b2cedd867d47a425be29759a357ccd5672c26653afb2bb0c8a08b3d58d3fd4043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Angiogenesis</topic><topic>Biomedical materials</topic><topic>Biomimetics</topic><topic>Bone biomaterials</topic><topic>Bone cements</topic><topic>Bone grafts</topic><topic>Bone growth</topic><topic>Calcium</topic><topic>Calcium phosphates</topic><topic>Chemical compounds</topic><topic>controlled drug release</topic><topic>Controlled release</topic><topic>Dosage</topic><topic>Drug delivery</topic><topic>Drug delivery systems</topic><topic>Drug development</topic><topic>Drug dosages</topic><topic>endothelial progenitor cells</topic><topic>Foams</topic><topic>Grafting</topic><topic>Immunosuppressive agents</topic><topic>Lipophilicity</topic><topic>Materials research</topic><topic>Materials science</topic><topic>Mesenchymal stem cells</topic><topic>Mineralization</topic><topic>Orthopedics</topic><topic>Osteogenesis</topic><topic>Pharmacology</topic><topic>rat mesenchymal stem cells</topic><topic>Regeneration</topic><topic>Regeneration (physiology)</topic><topic>Simvastatin</topic><topic>Substitute bone</topic><topic>Surgical implants</topic><topic>Tricalcium phosphate</topic><topic>Vascularization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khurana, Kanupriya</creatorcontrib><creatorcontrib>Guillem‐Marti, Jordi</creatorcontrib><creatorcontrib>Soldera, Flavio</creatorcontrib><creatorcontrib>Mücklich, Frank</creatorcontrib><creatorcontrib>Canal, Cristina</creatorcontrib><creatorcontrib>Ginebra, Maria‐Pau</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biomedical materials research. Part B, Applied biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khurana, Kanupriya</au><au>Guillem‐Marti, Jordi</au><au>Soldera, Flavio</au><au>Mücklich, Frank</au><au>Canal, Cristina</au><au>Ginebra, Maria‐Pau</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent</atitle><jtitle>Journal of biomedical materials research. Part B, Applied biomaterials</jtitle><addtitle>J Biomed Mater Res B Appl Biomater</addtitle><date>2020-04</date><risdate>2020</risdate><volume>108</volume><issue>3</issue><spage>760</spage><epage>770</epage><pages>760-770</pages><issn>1552-4973</issn><eissn>1552-4981</eissn><abstract>Apatitic bone cements have been used as a clinical bone substitutes and drug delivery vehicles for therapeutic agents in orthopedic applications. This has led to their combination with different drugs with known ability to foster bone formation. Recent studies have evaluated Simvastatin for its role in enhanced bone regeneration, but its lipophilicity hampers incorporation and release to and from the bone graft. In this study, injectable calcium phosphate foams (i‐CPF) based on α‐tricalcium phosphate were loaded for the first time with Pitavastatin. The stability of the drug in different conditions relevant to this study, the effect of the drug on the i‐CPFs properties, the release profile, and the in vitro biological performance with regard to mineralization and vascularization were investigated. Pitavastatin did not cause any changes in neither the micro nor the macro structure of the i‐CPFs, which retained their biomimetic features. PITA‐loaded i‐CPFs showed a dose‐dependent drug release, with early stage release kinetics clearly affected by the evolving microstructure due to the setting of cement. in vitro studies showed dose‐dependent enhancement of mineralization and vascularization. Our findings contribute towards the design of controlled release with low drug dosing bone grafts: i‐CPFs loaded with PITA as osteogenic and angiogenic agent.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>31187939</pmid><doi>10.1002/jbm.b.34430</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of biomedical materials research. Part B, Applied biomaterials, 2020-04, Vol.108 (3), p.760-770 |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Angiogenesis Biomedical materials Biomimetics Bone biomaterials Bone cements Bone grafts Bone growth Calcium Calcium phosphates Chemical compounds controlled drug release Controlled release Dosage Drug delivery Drug delivery systems Drug development Drug dosages endothelial progenitor cells Foams Grafting Immunosuppressive agents Lipophilicity Materials research Materials science Mesenchymal stem cells Mineralization Orthopedics Osteogenesis Pharmacology rat mesenchymal stem cells Regeneration Regeneration (physiology) Simvastatin Substitute bone Surgical implants Tricalcium phosphate Vascularization |
| title | Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent |
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