Dose-Dependent Sustained Release of Dexamethasone in Inner Ear Cochlear Fluids Using a Novel Local Delivery Approach
The thermo-reversible triblock copolymer poloxamer 407 was investigated as a drug delivery vehicle for micronized dexamethasone into the middle and inner ears of guinea pigs. The study characterized the gelation and in vitro release kinetics of poloxamer formulations. In vivo, the pharmacokinetic pr...
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| Veröffentlicht in: | Audiology & neurotology 2009-01, Vol.14 (6), p.393-401 |
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| creator | Wang, Xiaobo Dellamary, Luis Fernandez, Rayne Harrop, Anne Keithley, Elizabeth M. Harris, Jeffrey P. Ye, Qiang Lichter, Jay LeBel, Carl Piu, Fabrice |
| description | The thermo-reversible triblock copolymer poloxamer 407 was investigated as a drug delivery vehicle for micronized dexamethasone into the middle and inner ears of guinea pigs. The study characterized the gelation and in vitro release kinetics of poloxamer formulations. In vivo, the pharmacokinetic profile of formulations containing varying concentrations of poloxamer and dexamethasone was examined following intratympanic administration. Significant drug levels within the perilymph were observed for at least 10 days, while systemic exposure was minimal. The sustained-release kinetics profile could be significantly modulated by varying the concentrations of both poloxamer and dexamethasone. Assessment of auditory function revealed a small transient shift in hearing threshold, most probably of conductive nature, which resolved itself within a week. No significant histological changes of the round window membrane or cochlea could be noted. Poloxamer 407 thus represents an effective and safe delivery system to achieve sustained release of dexamethasone to the inner ear. |
| doi_str_mv | 10.1159/000241896 |
| format | Article |
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The study characterized the gelation and in vitro release kinetics of poloxamer formulations. In vivo, the pharmacokinetic profile of formulations containing varying concentrations of poloxamer and dexamethasone was examined following intratympanic administration. Significant drug levels within the perilymph were observed for at least 10 days, while systemic exposure was minimal. The sustained-release kinetics profile could be significantly modulated by varying the concentrations of both poloxamer and dexamethasone. Assessment of auditory function revealed a small transient shift in hearing threshold, most probably of conductive nature, which resolved itself within a week. No significant histological changes of the round window membrane or cochlea could be noted. Poloxamer 407 thus represents an effective and safe delivery system to achieve sustained release of dexamethasone to the inner ear.</description><identifier>ISSN: 1420-3030</identifier><identifier>ISBN: 9783805592888</identifier><identifier>ISBN: 3805592884</identifier><identifier>EISSN: 1421-9700</identifier><identifier>EISBN: 9783805592895</identifier><identifier>EISBN: 3805592892</identifier><identifier>DOI: 10.1159/000241896</identifier><identifier>PMID: 19923809</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>Analysis of Variance ; Animals ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Clinical outcomes ; Cochlea - drug effects ; Delayed-Action Preparations - administration & dosage ; Delayed-Action Preparations - pharmacokinetics ; Delivery. Postpartum. Lactation ; Dexamethasone - administration & dosage ; Dexamethasone - pharmacokinetics ; Dose-Response Relationship, Drug ; Drug Administration Routes ; Drug Carriers - administration & dosage ; Drug Carriers - pharmacokinetics ; Drug delivery systems ; Drug therapy ; Ear diseases ; Electrophysiology ; Evoked Potentials, Auditory, Brain Stem - physiology ; Female ; Guinea Pigs ; Gynecology. Andrology. Obstetrics ; Hearing - drug effects ; Hearing Tests ; Medical sciences ; Otorhinolaryngology. Stomatology ; Perilymph - drug effects ; Pharmacology ; Pharmacology. Drug treatments ; Poloxamer - administration & dosage ; Poloxamer - pharmacokinetics ; Rodents ; Tympanic Membrane - drug effects</subject><ispartof>Audiology & neurotology, 2009-01, Vol.14 (6), p.393-401</ispartof><rights>2009 S. Karger AG, Basel</rights><rights>2009 INIST-CNRS</rights><rights>(c) 2009 S. Karger AG, Basel.</rights><rights>Copyright (c) 2009 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-265d08a78a934f479020537174affbd7950152666387823458cecdd9bb64f28d3</citedby><cites>FETCH-LOGICAL-c459t-265d08a78a934f479020537174affbd7950152666387823458cecdd9bb64f28d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22108210$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19923809$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xiaobo</creatorcontrib><creatorcontrib>Dellamary, Luis</creatorcontrib><creatorcontrib>Fernandez, Rayne</creatorcontrib><creatorcontrib>Harrop, Anne</creatorcontrib><creatorcontrib>Keithley, Elizabeth M.</creatorcontrib><creatorcontrib>Harris, Jeffrey P.</creatorcontrib><creatorcontrib>Ye, Qiang</creatorcontrib><creatorcontrib>Lichter, Jay</creatorcontrib><creatorcontrib>LeBel, Carl</creatorcontrib><creatorcontrib>Piu, Fabrice</creatorcontrib><title>Dose-Dependent Sustained Release of Dexamethasone in Inner Ear Cochlear Fluids Using a Novel Local Delivery Approach</title><title>Audiology & neurotology</title><addtitle>Audiol Neurotol</addtitle><description>The thermo-reversible triblock copolymer poloxamer 407 was investigated as a drug delivery vehicle for micronized dexamethasone into the middle and inner ears of guinea pigs. The study characterized the gelation and in vitro release kinetics of poloxamer formulations. In vivo, the pharmacokinetic profile of formulations containing varying concentrations of poloxamer and dexamethasone was examined following intratympanic administration. Significant drug levels within the perilymph were observed for at least 10 days, while systemic exposure was minimal. The sustained-release kinetics profile could be significantly modulated by varying the concentrations of both poloxamer and dexamethasone. Assessment of auditory function revealed a small transient shift in hearing threshold, most probably of conductive nature, which resolved itself within a week. No significant histological changes of the round window membrane or cochlea could be noted. Poloxamer 407 thus represents an effective and safe delivery system to achieve sustained release of dexamethasone to the inner ear.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Clinical outcomes</subject><subject>Cochlea - drug effects</subject><subject>Delayed-Action Preparations - administration & dosage</subject><subject>Delayed-Action Preparations - pharmacokinetics</subject><subject>Delivery. Postpartum. Lactation</subject><subject>Dexamethasone - administration & dosage</subject><subject>Dexamethasone - pharmacokinetics</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Administration Routes</subject><subject>Drug Carriers - administration & dosage</subject><subject>Drug Carriers - pharmacokinetics</subject><subject>Drug delivery systems</subject><subject>Drug therapy</subject><subject>Ear diseases</subject><subject>Electrophysiology</subject><subject>Evoked Potentials, Auditory, Brain Stem - physiology</subject><subject>Female</subject><subject>Guinea Pigs</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Hearing - drug effects</subject><subject>Hearing Tests</subject><subject>Medical sciences</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Perilymph - drug effects</subject><subject>Pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Poloxamer - administration & dosage</subject><subject>Poloxamer - pharmacokinetics</subject><subject>Rodents</subject><subject>Tympanic Membrane - drug effects</subject><issn>1420-3030</issn><issn>1421-9700</issn><isbn>9783805592888</isbn><isbn>3805592884</isbn><isbn>9783805592895</isbn><isbn>3805592892</isbn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp90c1rFDEYBvD4ha21B-8iQdDSw-ibr0lyLLutFhYLas9DNvNOd-pssiYzxf73Rndp0UMPIYf88rwkDyGvGHxgTNmPAMAlM7Z-RA6tNsKAUpYbqx6TfSY5q6wGePLPmTFP_55BJUDAHnmR83WJUUrJ52SPWcuLtPtknMeM1Rw3GFoMI_025dH1AVv6FQd0GWns6Bx_uTWOK5djQNoHeh4CJnrqEp1Fvyou0bNh6ttML3MfrqijX-INDnQRvRvK9aG_wXRLTzabFJ1fvSTPOjdkPNztB-Ty7PT77HO1uPh0PjtZVF4qO1a8Vi0Yp42zQnZSW-CghGZauq5bttoqYIrXdS2MNlxIZTz6trXLZS07blpxQI62uWXszwnz2Kz77HEYXMA45UYLyaQuEUW-f1ByJkoDtS3w7X_wOk4plFc0nIOpOXBR0PEW-RRzTtg1m9SvXbptGDR_Gm3uGi32zS5wWq6xvZe7igp4twMul9_skgu-z3eOcwamrOJeb90Pl64w3YPtnN8gIKlY</recordid><startdate>20090101</startdate><enddate>20090101</enddate><creator>Wang, Xiaobo</creator><creator>Dellamary, Luis</creator><creator>Fernandez, Rayne</creator><creator>Harrop, Anne</creator><creator>Keithley, Elizabeth M.</creator><creator>Harris, Jeffrey P.</creator><creator>Ye, Qiang</creator><creator>Lichter, Jay</creator><creator>LeBel, Carl</creator><creator>Piu, Fabrice</creator><general>Karger</general><general>S. Karger AG</general><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20090101</creationdate><title>Dose-Dependent Sustained Release of Dexamethasone in Inner Ear Cochlear Fluids Using a Novel Local Delivery Approach</title><author>Wang, Xiaobo ; Dellamary, Luis ; Fernandez, Rayne ; Harrop, Anne ; Keithley, Elizabeth M. ; Harris, Jeffrey P. ; Ye, Qiang ; Lichter, Jay ; LeBel, Carl ; Piu, Fabrice</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-265d08a78a934f479020537174affbd7950152666387823458cecdd9bb64f28d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Clinical outcomes</topic><topic>Cochlea - drug effects</topic><topic>Delayed-Action Preparations - administration & dosage</topic><topic>Delayed-Action Preparations - pharmacokinetics</topic><topic>Delivery. Postpartum. Lactation</topic><topic>Dexamethasone - administration & dosage</topic><topic>Dexamethasone - pharmacokinetics</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Administration Routes</topic><topic>Drug Carriers - administration & dosage</topic><topic>Drug Carriers - pharmacokinetics</topic><topic>Drug delivery systems</topic><topic>Drug therapy</topic><topic>Ear diseases</topic><topic>Electrophysiology</topic><topic>Evoked Potentials, Auditory, Brain Stem - physiology</topic><topic>Female</topic><topic>Guinea Pigs</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Hearing - drug effects</topic><topic>Hearing Tests</topic><topic>Medical sciences</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Perilymph - drug effects</topic><topic>Pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Poloxamer - administration & dosage</topic><topic>Poloxamer - pharmacokinetics</topic><topic>Rodents</topic><topic>Tympanic Membrane - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xiaobo</creatorcontrib><creatorcontrib>Dellamary, Luis</creatorcontrib><creatorcontrib>Fernandez, Rayne</creatorcontrib><creatorcontrib>Harrop, Anne</creatorcontrib><creatorcontrib>Keithley, Elizabeth M.</creatorcontrib><creatorcontrib>Harris, Jeffrey P.</creatorcontrib><creatorcontrib>Ye, Qiang</creatorcontrib><creatorcontrib>Lichter, Jay</creatorcontrib><creatorcontrib>LeBel, Carl</creatorcontrib><creatorcontrib>Piu, Fabrice</creatorcontrib><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</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 Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</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>Psychology 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><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Audiology & neurotology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xiaobo</au><au>Dellamary, Luis</au><au>Fernandez, Rayne</au><au>Harrop, Anne</au><au>Keithley, Elizabeth M.</au><au>Harris, Jeffrey P.</au><au>Ye, Qiang</au><au>Lichter, Jay</au><au>LeBel, Carl</au><au>Piu, Fabrice</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dose-Dependent Sustained Release of Dexamethasone in Inner Ear Cochlear Fluids Using a Novel Local Delivery Approach</atitle><jtitle>Audiology & neurotology</jtitle><addtitle>Audiol Neurotol</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>14</volume><issue>6</issue><spage>393</spage><epage>401</epage><pages>393-401</pages><issn>1420-3030</issn><eissn>1421-9700</eissn><isbn>9783805592888</isbn><isbn>3805592884</isbn><eisbn>9783805592895</eisbn><eisbn>3805592892</eisbn><abstract>The thermo-reversible triblock copolymer poloxamer 407 was investigated as a drug delivery vehicle for micronized dexamethasone into the middle and inner ears of guinea pigs. The study characterized the gelation and in vitro release kinetics of poloxamer formulations. In vivo, the pharmacokinetic profile of formulations containing varying concentrations of poloxamer and dexamethasone was examined following intratympanic administration. Significant drug levels within the perilymph were observed for at least 10 days, while systemic exposure was minimal. The sustained-release kinetics profile could be significantly modulated by varying the concentrations of both poloxamer and dexamethasone. Assessment of auditory function revealed a small transient shift in hearing threshold, most probably of conductive nature, which resolved itself within a week. No significant histological changes of the round window membrane or cochlea could be noted. Poloxamer 407 thus represents an effective and safe delivery system to achieve sustained release of dexamethasone to the inner ear.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>19923809</pmid><doi>10.1159/000241896</doi><tpages>9</tpages></addata></record> |
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| ispartof | Audiology & neurotology, 2009-01, Vol.14 (6), p.393-401 |
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| subjects | Analysis of Variance Animals Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Clinical outcomes Cochlea - drug effects Delayed-Action Preparations - administration & dosage Delayed-Action Preparations - pharmacokinetics Delivery. Postpartum. Lactation Dexamethasone - administration & dosage Dexamethasone - pharmacokinetics Dose-Response Relationship, Drug Drug Administration Routes Drug Carriers - administration & dosage Drug Carriers - pharmacokinetics Drug delivery systems Drug therapy Ear diseases Electrophysiology Evoked Potentials, Auditory, Brain Stem - physiology Female Guinea Pigs Gynecology. Andrology. Obstetrics Hearing - drug effects Hearing Tests Medical sciences Otorhinolaryngology. Stomatology Perilymph - drug effects Pharmacology Pharmacology. Drug treatments Poloxamer - administration & dosage Poloxamer - pharmacokinetics Rodents Tympanic Membrane - drug effects |
| title | Dose-Dependent Sustained Release of Dexamethasone in Inner Ear Cochlear Fluids Using a Novel Local Delivery Approach |
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