Improved Lysozyme Stability and Release Properties of Poly(lactide-co-glycolide) Implants Prepared by Hot-Melt Extrusion
Purpose To assess the feasibility of hot-melt extrusion (HME) for preparing implants based on protein/poly(lactide-co-glycolide) (PLGA) formulations with special emphasis on protein stability, burst release and release completeness. Method Model protein (lysozyme)-loaded PLGA implants were prepared...
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| Veröffentlicht in: | Pharmaceutical research 2010-02, Vol.27 (2), p.371-379 |
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| creator | Ghalanbor, Zahra Körber, Martin Bodmeier, Roland |
| description | Purpose To assess the feasibility of hot-melt extrusion (HME) for preparing implants based on protein/poly(lactide-co-glycolide) (PLGA) formulations with special emphasis on protein stability, burst release and release completeness. Method Model protein (lysozyme)-loaded PLGA implants were prepared with a screw extruder and a self-built syringe-die device as a rapid screening tool for HME formulation optimization. Lysozyme stability was determined using DSC, FTIR, HPLC and biological activity. The simultaneous effect of lysozyme and PEG loadings was investigated to obtain optimized formulations with high drug loading but low initial release. Results Lysozyme was recovered from implants with full biological activity after HME. The release from all implants reached the 100% value in 60-80 days with nearly complete enzymatic activity of the last fraction of released lysozyme. Pure PLGA implants with up to 20% lysozyme loading could be formulated without initial burst. The incorporation of PEG 400 reduced the initial burst at drug loadings in excess of 20%. Conclusion A complete lysozyme recovery in active form with a burst-free and complete release from PLGA implants prepared by hot-melt extrusion was obtained. This is in contrast to many reported microparticulate lysozyme-PLGA systems and suggests the great potential of hot-melt extrusion for the preparation of protein-PLGA implants. |
| doi_str_mv | 10.1007/s11095-009-0033-x |
| format | Article |
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Method Model protein (lysozyme)-loaded PLGA implants were prepared with a screw extruder and a self-built syringe-die device as a rapid screening tool for HME formulation optimization. Lysozyme stability was determined using DSC, FTIR, HPLC and biological activity. The simultaneous effect of lysozyme and PEG loadings was investigated to obtain optimized formulations with high drug loading but low initial release. Results Lysozyme was recovered from implants with full biological activity after HME. The release from all implants reached the 100% value in 60-80 days with nearly complete enzymatic activity of the last fraction of released lysozyme. Pure PLGA implants with up to 20% lysozyme loading could be formulated without initial burst. The incorporation of PEG 400 reduced the initial burst at drug loadings in excess of 20%. Conclusion A complete lysozyme recovery in active form with a burst-free and complete release from PLGA implants prepared by hot-melt extrusion was obtained. This is in contrast to many reported microparticulate lysozyme-PLGA systems and suggests the great potential of hot-melt extrusion for the preparation of protein-PLGA implants.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-009-0033-x</identifier><identifier>PMID: 20033474</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>Boston: Boston : Springer US</publisher><subject>Absorbable Implants ; Biochemistry ; Biodegradable materials ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Delayed-Action Preparations - chemical synthesis ; Delayed-Action Preparations - pharmacokinetics ; Drug delivery systems ; Drug Delivery Systems - methods ; Enzyme Stability ; General pharmacology ; Hot Temperature ; Lactic Acid - chemical synthesis ; Lactic Acid - pharmacokinetics ; Medical Law ; Medical sciences ; Muramidase - chemical synthesis ; Muramidase - pharmacokinetics ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Pharmacy ; Polyglycolic Acid - chemical synthesis ; Polyglycolic Acid - pharmacokinetics ; Proteins ; Research Paper ; Transplants & implants</subject><ispartof>Pharmaceutical research, 2010-02, Vol.27 (2), p.371-379</ispartof><rights>Springer Science+Business Media, LLC 2009</rights><rights>2015 INIST-CNRS</rights><rights>Springer Science+Business Media, LLC 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-9f66553d243801a1d20cfa3c79ffb046410afcb6b5badc727d2ccdae2d81e4fb3</citedby><cites>FETCH-LOGICAL-c424t-9f66553d243801a1d20cfa3c79ffb046410afcb6b5badc727d2ccdae2d81e4fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11095-009-0033-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11095-009-0033-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22546423$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20033474$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ghalanbor, Zahra</creatorcontrib><creatorcontrib>Körber, Martin</creatorcontrib><creatorcontrib>Bodmeier, Roland</creatorcontrib><title>Improved Lysozyme Stability and Release Properties of Poly(lactide-co-glycolide) Implants Prepared by Hot-Melt Extrusion</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>Purpose To assess the feasibility of hot-melt extrusion (HME) for preparing implants based on protein/poly(lactide-co-glycolide) (PLGA) formulations with special emphasis on protein stability, burst release and release completeness. Method Model protein (lysozyme)-loaded PLGA implants were prepared with a screw extruder and a self-built syringe-die device as a rapid screening tool for HME formulation optimization. Lysozyme stability was determined using DSC, FTIR, HPLC and biological activity. The simultaneous effect of lysozyme and PEG loadings was investigated to obtain optimized formulations with high drug loading but low initial release. Results Lysozyme was recovered from implants with full biological activity after HME. The release from all implants reached the 100% value in 60-80 days with nearly complete enzymatic activity of the last fraction of released lysozyme. Pure PLGA implants with up to 20% lysozyme loading could be formulated without initial burst. The incorporation of PEG 400 reduced the initial burst at drug loadings in excess of 20%. Conclusion A complete lysozyme recovery in active form with a burst-free and complete release from PLGA implants prepared by hot-melt extrusion was obtained. This is in contrast to many reported microparticulate lysozyme-PLGA systems and suggests the great potential of hot-melt extrusion for the preparation of protein-PLGA implants.</description><subject>Absorbable Implants</subject><subject>Biochemistry</subject><subject>Biodegradable materials</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Delayed-Action Preparations - chemical synthesis</subject><subject>Delayed-Action Preparations - pharmacokinetics</subject><subject>Drug delivery systems</subject><subject>Drug Delivery Systems - methods</subject><subject>Enzyme Stability</subject><subject>General pharmacology</subject><subject>Hot Temperature</subject><subject>Lactic Acid - chemical synthesis</subject><subject>Lactic Acid - pharmacokinetics</subject><subject>Medical Law</subject><subject>Medical sciences</subject><subject>Muramidase - chemical synthesis</subject><subject>Muramidase - pharmacokinetics</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Polyglycolic Acid - chemical synthesis</subject><subject>Polyglycolic Acid - pharmacokinetics</subject><subject>Proteins</subject><subject>Research Paper</subject><subject>Transplants & implants</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kEuLFDEUhYMoTtv6A9xoEARdRG8eVelayjA6Ay0OjgPuQiqPpoZ0pSdJS5e_3jTVOjsXIYT7nXNuDkIvKXygAPJjphS6hgB09XBODo_QgjaSkw7Ez8doAZIJspKCnqFnOd8BwIp24ik6Y0dcSLFAh6vtLsVfzuL1lOPvaevwTdH9EIYyYT1a_N0Fp7PD1ynuXCqDyzh6fB3D9C5oUwbriIlkEyYTQ328x9Uw6LHkqnA7napzP-HLWMhXFwq-OJS0z0Mcn6MnXofsXpzuJbr9fPHj_JKsv325Ov-0JkYwUUjn27ZpuGWCr4BqahkYr7mRnfc9iFZQ0N70bd_02hrJpGXGWO2YXVEnfM-X6M3sW795v3e5qLu4T2ONVIwxCS2tVSwRnSGTYs7JebVLw1anSVFQx6rVXLWqVatjd-pQNa9Oxvt-6-w_xd9uK_D2BOhsdPBJj2bIDxxr6vrsGM5mLtfRuHHpYcP_pb-eRV5HpTepGt_eMKAcqOxk1zL-BxqpofM</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Ghalanbor, Zahra</creator><creator>Körber, Martin</creator><creator>Bodmeier, Roland</creator><general>Boston : Springer US</general><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>FBQ</scope><scope>IQODW</scope><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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20100201</creationdate><title>Improved Lysozyme Stability and Release Properties of Poly(lactide-co-glycolide) Implants Prepared by Hot-Melt Extrusion</title><author>Ghalanbor, Zahra ; Körber, Martin ; Bodmeier, Roland</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-9f66553d243801a1d20cfa3c79ffb046410afcb6b5badc727d2ccdae2d81e4fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Absorbable Implants</topic><topic>Biochemistry</topic><topic>Biodegradable materials</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Delayed-Action Preparations - chemical synthesis</topic><topic>Delayed-Action Preparations - pharmacokinetics</topic><topic>Drug delivery systems</topic><topic>Drug Delivery Systems - methods</topic><topic>Enzyme Stability</topic><topic>General pharmacology</topic><topic>Hot Temperature</topic><topic>Lactic Acid - chemical synthesis</topic><topic>Lactic Acid - pharmacokinetics</topic><topic>Medical Law</topic><topic>Medical sciences</topic><topic>Muramidase - chemical synthesis</topic><topic>Muramidase - pharmacokinetics</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Polyglycolic Acid - chemical synthesis</topic><topic>Polyglycolic Acid - pharmacokinetics</topic><topic>Proteins</topic><topic>Research Paper</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ghalanbor, Zahra</creatorcontrib><creatorcontrib>Körber, Martin</creatorcontrib><creatorcontrib>Bodmeier, Roland</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ghalanbor, Zahra</au><au>Körber, Martin</au><au>Bodmeier, Roland</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improved Lysozyme Stability and Release Properties of Poly(lactide-co-glycolide) Implants Prepared by Hot-Melt Extrusion</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2010-02-01</date><risdate>2010</risdate><volume>27</volume><issue>2</issue><spage>371</spage><epage>379</epage><pages>371-379</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Purpose To assess the feasibility of hot-melt extrusion (HME) for preparing implants based on protein/poly(lactide-co-glycolide) (PLGA) formulations with special emphasis on protein stability, burst release and release completeness. Method Model protein (lysozyme)-loaded PLGA implants were prepared with a screw extruder and a self-built syringe-die device as a rapid screening tool for HME formulation optimization. Lysozyme stability was determined using DSC, FTIR, HPLC and biological activity. The simultaneous effect of lysozyme and PEG loadings was investigated to obtain optimized formulations with high drug loading but low initial release. Results Lysozyme was recovered from implants with full biological activity after HME. The release from all implants reached the 100% value in 60-80 days with nearly complete enzymatic activity of the last fraction of released lysozyme. Pure PLGA implants with up to 20% lysozyme loading could be formulated without initial burst. The incorporation of PEG 400 reduced the initial burst at drug loadings in excess of 20%. Conclusion A complete lysozyme recovery in active form with a burst-free and complete release from PLGA implants prepared by hot-melt extrusion was obtained. This is in contrast to many reported microparticulate lysozyme-PLGA systems and suggests the great potential of hot-melt extrusion for the preparation of protein-PLGA implants.</abstract><cop>Boston</cop><pub>Boston : Springer US</pub><pmid>20033474</pmid><doi>10.1007/s11095-009-0033-x</doi><tpages>9</tpages></addata></record> |
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| subjects | Absorbable Implants Biochemistry Biodegradable materials Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Delayed-Action Preparations - chemical synthesis Delayed-Action Preparations - pharmacokinetics Drug delivery systems Drug Delivery Systems - methods Enzyme Stability General pharmacology Hot Temperature Lactic Acid - chemical synthesis Lactic Acid - pharmacokinetics Medical Law Medical sciences Muramidase - chemical synthesis Muramidase - pharmacokinetics Pharmaceutical technology. Pharmaceutical industry Pharmacology Pharmacology. Drug treatments Pharmacology/Toxicology Pharmacy Polyglycolic Acid - chemical synthesis Polyglycolic Acid - pharmacokinetics Proteins Research Paper Transplants & implants |
| title | Improved Lysozyme Stability and Release Properties of Poly(lactide-co-glycolide) Implants Prepared by Hot-Melt Extrusion |
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