Local drug delivery using poly(lactic-co-glycolic acid) nanoparticles in thermosensitive gels for inner ear disease treatment
Intratympanic (IT) therapies have been explored to address several side effects that could be caused by systemic administration of steroids to treat inner ear diseases. For effective drug delivery to the inner ear, an IT delivery system was developed using poly(lactic-co-glycolic acid) (PLGA) nanopa...
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| Veröffentlicht in: | Drug delivery 2021-01, Vol.28 (1), p.2268-2277 |
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| creator | Kim, Dong-Hyun Nguyen, Thu Nhan Han, Young-Min Tran, Phuong Rho, Jinhyung Lee, Jae-Young Son, Hwa-Young Park, Jeong-Sook |
| description | Intratympanic (IT) therapies have been explored to address several side effects that could be caused by systemic administration of steroids to treat inner ear diseases. For effective drug delivery to the inner ear, an IT delivery system was developed using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and thermosensitive gels to maintain sustained release. Dexamethasone (DEX) was used as a model drug. The size and zeta potential of PLGA NPs and the gelation time of the thermosensitive gel were measured. In vitro drug release was studied using a Franz diffusion cell. Cytotoxicity of the formulations was investigated using SK-MEL-31 cells. Inflammatory responses were evaluated by histological observation of spiral ganglion cells and stria vascularis in the mouse cochlea 24 h after IT administration. In addition, the biodistribution of the formulations in mouse ears was observed by fluorescence imaging using coumarin-6. DEX-NPs showed a particle size of 150.0 ± 3.2 nm in diameter and a zeta potential of −18.7 ± 0.6. The DEX-NP-gel showed a gelation time of approximately 64 s at 37 °C and presented a similar release profile and cytotoxicity as that for DEX-NP. Furthermore, no significant inflammatory response was observed after IT administration. Fluorescence imaging results suggested that DEX-NP-gel sustained release compared to the other formulations. In conclusion, the PLGA NP-loaded thermosensitive gel may be a potential drug delivery system for the inner ear. |
| doi_str_mv | 10.1080/10717544.2021.1992041 |
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For effective drug delivery to the inner ear, an IT delivery system was developed using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and thermosensitive gels to maintain sustained release. Dexamethasone (DEX) was used as a model drug. The size and zeta potential of PLGA NPs and the gelation time of the thermosensitive gel were measured. In vitro drug release was studied using a Franz diffusion cell. Cytotoxicity of the formulations was investigated using SK-MEL-31 cells. Inflammatory responses were evaluated by histological observation of spiral ganglion cells and stria vascularis in the mouse cochlea 24 h after IT administration. In addition, the biodistribution of the formulations in mouse ears was observed by fluorescence imaging using coumarin-6. DEX-NPs showed a particle size of 150.0 ± 3.2 nm in diameter and a zeta potential of −18.7 ± 0.6. The DEX-NP-gel showed a gelation time of approximately 64 s at 37 °C and presented a similar release profile and cytotoxicity as that for DEX-NP. Furthermore, no significant inflammatory response was observed after IT administration. Fluorescence imaging results suggested that DEX-NP-gel sustained release compared to the other formulations. In conclusion, the PLGA NP-loaded thermosensitive gel may be a potential drug delivery system for the inner ear.</description><identifier>ISSN: 1071-7544</identifier><identifier>EISSN: 1521-0464</identifier><identifier>DOI: 10.1080/10717544.2021.1992041</identifier><identifier>PMID: 34668836</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Animals ; Anti-Inflammatory Agents - administration & dosage ; Anti-Inflammatory Agents - pharmacokinetics ; Anti-Inflammatory Agents - pharmacology ; Cell Survival ; Chemistry, Pharmaceutical ; Cytotoxicity ; dexamethasone ; Dexamethasone - administration & dosage ; Dexamethasone - pharmacokinetics ; Dexamethasone - pharmacology ; Drug Carriers - chemistry ; Drug delivery systems ; Drug Liberation ; Drug Stability ; Hydrogels - chemistry ; Inner ear drug delivery ; intratympanic administration ; Labyrinth Diseases - drug therapy ; Male ; Mice ; Mice, Inbred BALB C ; Nanoparticles ; Nanoparticles - chemistry ; Particle Size ; PLGA nanoparticles ; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry ; Steroids ; Surface Properties ; thermosensitive gel</subject><ispartof>Drug delivery, 2021-01, Vol.28 (1), p.2268-2277</ispartof><rights>2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2021</rights><rights>2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution – Non-Commercial License http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2021 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-397f479331fda6fc15f3d2a140384bc6771358f79357fa36280ee5be2c6c7fe3</citedby><cites>FETCH-LOGICAL-c562t-397f479331fda6fc15f3d2a140384bc6771358f79357fa36280ee5be2c6c7fe3</cites><orcidid>0000-0002-4081-213X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530482/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530482/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,27479,27901,27902,53766,53768,59116,59117</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34668836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Dong-Hyun</creatorcontrib><creatorcontrib>Nguyen, Thu Nhan</creatorcontrib><creatorcontrib>Han, Young-Min</creatorcontrib><creatorcontrib>Tran, Phuong</creatorcontrib><creatorcontrib>Rho, Jinhyung</creatorcontrib><creatorcontrib>Lee, Jae-Young</creatorcontrib><creatorcontrib>Son, Hwa-Young</creatorcontrib><creatorcontrib>Park, Jeong-Sook</creatorcontrib><title>Local drug delivery using poly(lactic-co-glycolic acid) nanoparticles in thermosensitive gels for inner ear disease treatment</title><title>Drug delivery</title><addtitle>Drug Deliv</addtitle><description>Intratympanic (IT) therapies have been explored to address several side effects that could be caused by systemic administration of steroids to treat inner ear diseases. For effective drug delivery to the inner ear, an IT delivery system was developed using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and thermosensitive gels to maintain sustained release. Dexamethasone (DEX) was used as a model drug. The size and zeta potential of PLGA NPs and the gelation time of the thermosensitive gel were measured. In vitro drug release was studied using a Franz diffusion cell. Cytotoxicity of the formulations was investigated using SK-MEL-31 cells. Inflammatory responses were evaluated by histological observation of spiral ganglion cells and stria vascularis in the mouse cochlea 24 h after IT administration. In addition, the biodistribution of the formulations in mouse ears was observed by fluorescence imaging using coumarin-6. DEX-NPs showed a particle size of 150.0 ± 3.2 nm in diameter and a zeta potential of −18.7 ± 0.6. The DEX-NP-gel showed a gelation time of approximately 64 s at 37 °C and presented a similar release profile and cytotoxicity as that for DEX-NP. Furthermore, no significant inflammatory response was observed after IT administration. Fluorescence imaging results suggested that DEX-NP-gel sustained release compared to the other formulations. In conclusion, the PLGA NP-loaded thermosensitive gel may be a potential drug delivery system for the inner ear.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - administration & dosage</subject><subject>Anti-Inflammatory Agents - pharmacokinetics</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Cell Survival</subject><subject>Chemistry, Pharmaceutical</subject><subject>Cytotoxicity</subject><subject>dexamethasone</subject><subject>Dexamethasone - administration & dosage</subject><subject>Dexamethasone - pharmacokinetics</subject><subject>Dexamethasone - pharmacology</subject><subject>Drug Carriers - chemistry</subject><subject>Drug delivery systems</subject><subject>Drug Liberation</subject><subject>Drug Stability</subject><subject>Hydrogels - chemistry</subject><subject>Inner ear drug delivery</subject><subject>intratympanic administration</subject><subject>Labyrinth Diseases - drug therapy</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Particle Size</subject><subject>PLGA nanoparticles</subject><subject>Polylactic Acid-Polyglycolic Acid Copolymer - chemistry</subject><subject>Steroids</subject><subject>Surface Properties</subject><subject>thermosensitive gel</subject><issn>1071-7544</issn><issn>1521-0464</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNp9kktv1DAUhSMEoqXwE0CW2JRFBr_jbBCo4lFpJDbdWx77JvXIsQc7KZoF_x0PM60oC1a2fL57fK99muY1wSuCFX5PcEc6wfmKYkpWpO8p5uRJc04EJS3mkj-t-8q0B-iseVHKFmOsCBXPmzPGpVSKyfPm1zpZE5DLy4gcBH8HeY-W4uOIdinsL4Oxs7etTe0Y9jYFb5Gx3r1D0cS0M7mKAQryEc23kKdUIBY_Vxs0QihoSLlqETICk5HzBUwBNGcw8wRxftk8G0wo8Oq0XjQ3Xz7fXH1r19-_Xl99WrdWSDq3rO8G3vWMkcEZOVgiBuaoIRwzxTdWdh1hQg2VEN1gmKQKA4gNUCttNwC7aK6Pti6Zrd5lP5m818l4_ecg5VGfJtFKOgd9jw3mjkO_MYbKTe8IYRyYsLJ6fTh67ZbNBM7WKbIJj0wfK9Hf6jHdaSUY5opWg8uTQU4_FiiznnyxEIKJkJaiqVAcE0VEX9G3_6DbtORYX0pT2deeFFG8UuJI2ZxKyTA8NEOwPmRF32dFH7KiT1mpdW_-nuSh6j4cFfh4BHys_ziZnykHp2ezDykP2UTri2b_v-M35hrQDw</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Kim, Dong-Hyun</creator><creator>Nguyen, Thu Nhan</creator><creator>Han, Young-Min</creator><creator>Tran, Phuong</creator><creator>Rho, Jinhyung</creator><creator>Lee, Jae-Young</creator><creator>Son, Hwa-Young</creator><creator>Park, Jeong-Sook</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><general>Taylor & Francis Group</general><scope>0YH</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>7X7</scope><scope>7XB</scope><scope>88I</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>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M2P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-4081-213X</orcidid></search><sort><creationdate>20210101</creationdate><title>Local drug delivery using poly(lactic-co-glycolic acid) nanoparticles in thermosensitive gels for inner ear disease treatment</title><author>Kim, Dong-Hyun ; Nguyen, Thu Nhan ; Han, Young-Min ; Tran, Phuong ; Rho, Jinhyung ; Lee, Jae-Young ; Son, Hwa-Young ; Park, Jeong-Sook</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-397f479331fda6fc15f3d2a140384bc6771358f79357fa36280ee5be2c6c7fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - administration & dosage</topic><topic>Anti-Inflammatory Agents - pharmacokinetics</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Cell Survival</topic><topic>Chemistry, Pharmaceutical</topic><topic>Cytotoxicity</topic><topic>dexamethasone</topic><topic>Dexamethasone - administration & dosage</topic><topic>Dexamethasone - pharmacokinetics</topic><topic>Dexamethasone - pharmacology</topic><topic>Drug Carriers - chemistry</topic><topic>Drug delivery systems</topic><topic>Drug Liberation</topic><topic>Drug Stability</topic><topic>Hydrogels - chemistry</topic><topic>Inner ear drug delivery</topic><topic>intratympanic administration</topic><topic>Labyrinth Diseases - drug therapy</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Nanoparticles</topic><topic>Nanoparticles - chemistry</topic><topic>Particle Size</topic><topic>PLGA nanoparticles</topic><topic>Polylactic Acid-Polyglycolic Acid Copolymer - chemistry</topic><topic>Steroids</topic><topic>Surface Properties</topic><topic>thermosensitive gel</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Dong-Hyun</creatorcontrib><creatorcontrib>Nguyen, Thu Nhan</creatorcontrib><creatorcontrib>Han, Young-Min</creatorcontrib><creatorcontrib>Tran, Phuong</creatorcontrib><creatorcontrib>Rho, Jinhyung</creatorcontrib><creatorcontrib>Lee, Jae-Young</creatorcontrib><creatorcontrib>Son, Hwa-Young</creatorcontrib><creatorcontrib>Park, Jeong-Sook</creatorcontrib><collection>Taylor & Francis Open Access</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Science Database (Alumni Edition)</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Publicly Available Content Database</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 Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Drug delivery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Dong-Hyun</au><au>Nguyen, Thu Nhan</au><au>Han, Young-Min</au><au>Tran, Phuong</au><au>Rho, Jinhyung</au><au>Lee, Jae-Young</au><au>Son, Hwa-Young</au><au>Park, Jeong-Sook</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Local drug delivery using poly(lactic-co-glycolic acid) nanoparticles in thermosensitive gels for inner ear disease treatment</atitle><jtitle>Drug delivery</jtitle><addtitle>Drug Deliv</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>28</volume><issue>1</issue><spage>2268</spage><epage>2277</epage><pages>2268-2277</pages><issn>1071-7544</issn><eissn>1521-0464</eissn><abstract>Intratympanic (IT) therapies have been explored to address several side effects that could be caused by systemic administration of steroids to treat inner ear diseases. For effective drug delivery to the inner ear, an IT delivery system was developed using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and thermosensitive gels to maintain sustained release. Dexamethasone (DEX) was used as a model drug. The size and zeta potential of PLGA NPs and the gelation time of the thermosensitive gel were measured. In vitro drug release was studied using a Franz diffusion cell. Cytotoxicity of the formulations was investigated using SK-MEL-31 cells. Inflammatory responses were evaluated by histological observation of spiral ganglion cells and stria vascularis in the mouse cochlea 24 h after IT administration. In addition, the biodistribution of the formulations in mouse ears was observed by fluorescence imaging using coumarin-6. DEX-NPs showed a particle size of 150.0 ± 3.2 nm in diameter and a zeta potential of −18.7 ± 0.6. The DEX-NP-gel showed a gelation time of approximately 64 s at 37 °C and presented a similar release profile and cytotoxicity as that for DEX-NP. Furthermore, no significant inflammatory response was observed after IT administration. Fluorescence imaging results suggested that DEX-NP-gel sustained release compared to the other formulations. In conclusion, the PLGA NP-loaded thermosensitive gel may be a potential drug delivery system for the inner ear.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>34668836</pmid><doi>10.1080/10717544.2021.1992041</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-4081-213X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Anti-Inflammatory Agents - administration & dosage Anti-Inflammatory Agents - pharmacokinetics Anti-Inflammatory Agents - pharmacology Cell Survival Chemistry, Pharmaceutical Cytotoxicity dexamethasone Dexamethasone - administration & dosage Dexamethasone - pharmacokinetics Dexamethasone - pharmacology Drug Carriers - chemistry Drug delivery systems Drug Liberation Drug Stability Hydrogels - chemistry Inner ear drug delivery intratympanic administration Labyrinth Diseases - drug therapy Male Mice Mice, Inbred BALB C Nanoparticles Nanoparticles - chemistry Particle Size PLGA nanoparticles Polylactic Acid-Polyglycolic Acid Copolymer - chemistry Steroids Surface Properties thermosensitive gel |
| title | Local drug delivery using poly(lactic-co-glycolic acid) nanoparticles in thermosensitive gels for inner ear disease treatment |
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