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Design, development, and characterization of an idebenone-loaded poly-ε-caprolactone intravitreal implant as a new therapeutic approach for LHON treatment
[Display omitted] Leber's Hereditary Optic Neuropathy (LHON) is a hereditary mitochondrial neurodegenerative disease of unclear etiology and lack of available therapeutic alternatives. The main goal of the current pilot study was based on the evaluation of the feasibility and characteristics of...
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Published in: | European journal of pharmaceutics and biopharmaceutics 2021-11, Vol.168, p.195-207 |
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container_title | European journal of pharmaceutics and biopharmaceutics |
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creator | Varela-Fernández, Rubén Lema-Gesto, María Isabel González-Barcia, Miguel Otero-Espinar, Francisco Javier |
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Leber's Hereditary Optic Neuropathy (LHON) is a hereditary mitochondrial neurodegenerative disease of unclear etiology and lack of available therapeutic alternatives. The main goal of the current pilot study was based on the evaluation of the feasibility and characteristics of prolonged and controlled idebenone release from a PCL intravitreal implant. The design, development, and characterization of idebenone-loaded PCL implants prepared by an homogenization/extrusion/solvent evaporation method allowed the obtention of high PY, EE and LC values. In vitro characterization was completed by the assessment of mechanical and instrumental properties. The in vitro release of idebenone from the PCL implants was assessed and the implant erosion was monitored by the mass loss and surface morphology changes. DSC was used to estimate stability and interaction among implant’s components. The present work demonstrated the controlled and prolonged idebenone delivery from the PCL implants in an in vitro model. A consistent preclinical base was established, supporting the idea of idebenone-loaded PCL implants as a new strategy of long-term sustained intraocular delivery for the LHON treatment. |
doi_str_mv | 10.1016/j.ejpb.2021.09.001 |
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Leber's Hereditary Optic Neuropathy (LHON) is a hereditary mitochondrial neurodegenerative disease of unclear etiology and lack of available therapeutic alternatives. The main goal of the current pilot study was based on the evaluation of the feasibility and characteristics of prolonged and controlled idebenone release from a PCL intravitreal implant. The design, development, and characterization of idebenone-loaded PCL implants prepared by an homogenization/extrusion/solvent evaporation method allowed the obtention of high PY, EE and LC values. In vitro characterization was completed by the assessment of mechanical and instrumental properties. The in vitro release of idebenone from the PCL implants was assessed and the implant erosion was monitored by the mass loss and surface morphology changes. DSC was used to estimate stability and interaction among implant’s components. The present work demonstrated the controlled and prolonged idebenone delivery from the PCL implants in an in vitro model. A consistent preclinical base was established, supporting the idea of idebenone-loaded PCL implants as a new strategy of long-term sustained intraocular delivery for the LHON treatment.</description><identifier>ISSN: 0939-6411</identifier><identifier>EISSN: 1873-3441</identifier><identifier>DOI: 10.1016/j.ejpb.2021.09.001</identifier><identifier>PMID: 34500025</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Chemistry, Pharmaceutical - methods ; Chickens ; Chorioallantoic Membrane - drug effects ; Controlled drug delivery ; Delayed-Action Preparations ; Drug Carriers - chemistry ; Drug Delivery Systems ; Drug Implants ; Drug Stability ; Idebenone ; Intravitreal administration ; LHON ; Optic Atrophy, Hereditary, Leber - drug therapy ; Pilot Projects ; Poly-ε-caprolactone ; Polyesters - chemistry ; Polymeric implant ; Ubiquinone - administration & dosage ; Ubiquinone - analogs & derivatives ; Ubiquinone - chemistry</subject><ispartof>European journal of pharmaceutics and biopharmaceutics, 2021-11, Vol.168, p.195-207</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-a1b08fcea641f3cc744fce5f07658343773d6043c1d276edd03ea98c6185c93c3</citedby><cites>FETCH-LOGICAL-c400t-a1b08fcea641f3cc744fce5f07658343773d6043c1d276edd03ea98c6185c93c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34500025$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Varela-Fernández, Rubén</creatorcontrib><creatorcontrib>Lema-Gesto, María Isabel</creatorcontrib><creatorcontrib>González-Barcia, Miguel</creatorcontrib><creatorcontrib>Otero-Espinar, Francisco Javier</creatorcontrib><title>Design, development, and characterization of an idebenone-loaded poly-ε-caprolactone intravitreal implant as a new therapeutic approach for LHON treatment</title><title>European journal of pharmaceutics and biopharmaceutics</title><addtitle>Eur J Pharm Biopharm</addtitle><description>[Display omitted]
Leber's Hereditary Optic Neuropathy (LHON) is a hereditary mitochondrial neurodegenerative disease of unclear etiology and lack of available therapeutic alternatives. The main goal of the current pilot study was based on the evaluation of the feasibility and characteristics of prolonged and controlled idebenone release from a PCL intravitreal implant. The design, development, and characterization of idebenone-loaded PCL implants prepared by an homogenization/extrusion/solvent evaporation method allowed the obtention of high PY, EE and LC values. In vitro characterization was completed by the assessment of mechanical and instrumental properties. The in vitro release of idebenone from the PCL implants was assessed and the implant erosion was monitored by the mass loss and surface morphology changes. DSC was used to estimate stability and interaction among implant’s components. The present work demonstrated the controlled and prolonged idebenone delivery from the PCL implants in an in vitro model. A consistent preclinical base was established, supporting the idea of idebenone-loaded PCL implants as a new strategy of long-term sustained intraocular delivery for the LHON treatment.</description><subject>Animals</subject><subject>Chemistry, Pharmaceutical - methods</subject><subject>Chickens</subject><subject>Chorioallantoic Membrane - drug effects</subject><subject>Controlled drug delivery</subject><subject>Delayed-Action Preparations</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Delivery Systems</subject><subject>Drug Implants</subject><subject>Drug Stability</subject><subject>Idebenone</subject><subject>Intravitreal administration</subject><subject>LHON</subject><subject>Optic Atrophy, Hereditary, Leber - drug therapy</subject><subject>Pilot Projects</subject><subject>Poly-ε-caprolactone</subject><subject>Polyesters - chemistry</subject><subject>Polymeric implant</subject><subject>Ubiquinone - administration & dosage</subject><subject>Ubiquinone - analogs & derivatives</subject><subject>Ubiquinone - chemistry</subject><issn>0939-6411</issn><issn>1873-3441</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kU2O1DAQhS0EYpqBC7BAXrKYBDt2Ekdig4afQWoxG1hb1XaFdiuxg-1uNFyFc3ANzoSjHliyssr13tMrfYQ856zmjHevDjUell3dsIbXbKgZ4w_IhqteVEJK_pBs2CCGqpOcX5AnKR0YY7Jv1WNyIWRbhqbdkJ9vMbmv_opaPOEUlhl9vqLgLTV7iGAyRvcDsguehrH8U2dxhz54rKYAFi1dwnRX_f5VGVhimIqj7KjzOcLJ5YgwUTcvE_hMIVGgHr_TvMcICx6zMxSWYgOzp2OIdHtz-4muprz2eEoejTAlfHb_XpIv7999vr6ptrcfPl6_2VZGMpYr4DumRoNQLh2FMb2UZWpH1netElL0vbAdk8Jw2_QdWssEwqBMx1VrBmHEJXl5zi1Nvh0xZT27ZHAqpTEck27ang-NUqop0uYsNTGkFHHUS3QzxDvNmV6h6INeoegVimaDLlCK6cV9_nE3o_1n-UuhCF6fBViuPDmMOhmH3qB1EU3WNrj_5f8BZE6hWA</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Varela-Fernández, Rubén</creator><creator>Lema-Gesto, María Isabel</creator><creator>González-Barcia, Miguel</creator><creator>Otero-Espinar, Francisco Javier</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>202111</creationdate><title>Design, development, and characterization of an idebenone-loaded poly-ε-caprolactone intravitreal implant as a new therapeutic approach for LHON treatment</title><author>Varela-Fernández, Rubén ; Lema-Gesto, María Isabel ; González-Barcia, Miguel ; Otero-Espinar, Francisco Javier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-a1b08fcea641f3cc744fce5f07658343773d6043c1d276edd03ea98c6185c93c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Chemistry, Pharmaceutical - methods</topic><topic>Chickens</topic><topic>Chorioallantoic Membrane - drug effects</topic><topic>Controlled drug delivery</topic><topic>Delayed-Action Preparations</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Delivery Systems</topic><topic>Drug Implants</topic><topic>Drug Stability</topic><topic>Idebenone</topic><topic>Intravitreal administration</topic><topic>LHON</topic><topic>Optic Atrophy, Hereditary, Leber - drug therapy</topic><topic>Pilot Projects</topic><topic>Poly-ε-caprolactone</topic><topic>Polyesters - chemistry</topic><topic>Polymeric implant</topic><topic>Ubiquinone - administration & dosage</topic><topic>Ubiquinone - analogs & derivatives</topic><topic>Ubiquinone - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Varela-Fernández, Rubén</creatorcontrib><creatorcontrib>Lema-Gesto, María Isabel</creatorcontrib><creatorcontrib>González-Barcia, Miguel</creatorcontrib><creatorcontrib>Otero-Espinar, Francisco Javier</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect: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>MEDLINE - Academic</collection><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Varela-Fernández, Rubén</au><au>Lema-Gesto, María Isabel</au><au>González-Barcia, Miguel</au><au>Otero-Espinar, Francisco Javier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, development, and characterization of an idebenone-loaded poly-ε-caprolactone intravitreal implant as a new therapeutic approach for LHON treatment</atitle><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle><addtitle>Eur J Pharm Biopharm</addtitle><date>2021-11</date><risdate>2021</risdate><volume>168</volume><spage>195</spage><epage>207</epage><pages>195-207</pages><issn>0939-6411</issn><eissn>1873-3441</eissn><abstract>[Display omitted]
Leber's Hereditary Optic Neuropathy (LHON) is a hereditary mitochondrial neurodegenerative disease of unclear etiology and lack of available therapeutic alternatives. The main goal of the current pilot study was based on the evaluation of the feasibility and characteristics of prolonged and controlled idebenone release from a PCL intravitreal implant. The design, development, and characterization of idebenone-loaded PCL implants prepared by an homogenization/extrusion/solvent evaporation method allowed the obtention of high PY, EE and LC values. In vitro characterization was completed by the assessment of mechanical and instrumental properties. The in vitro release of idebenone from the PCL implants was assessed and the implant erosion was monitored by the mass loss and surface morphology changes. DSC was used to estimate stability and interaction among implant’s components. The present work demonstrated the controlled and prolonged idebenone delivery from the PCL implants in an in vitro model. A consistent preclinical base was established, supporting the idea of idebenone-loaded PCL implants as a new strategy of long-term sustained intraocular delivery for the LHON treatment.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34500025</pmid><doi>10.1016/j.ejpb.2021.09.001</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Chemistry, Pharmaceutical - methods Chickens Chorioallantoic Membrane - drug effects Controlled drug delivery Delayed-Action Preparations Drug Carriers - chemistry Drug Delivery Systems Drug Implants Drug Stability Idebenone Intravitreal administration LHON Optic Atrophy, Hereditary, Leber - drug therapy Pilot Projects Poly-ε-caprolactone Polyesters - chemistry Polymeric implant Ubiquinone - administration & dosage Ubiquinone - analogs & derivatives Ubiquinone - chemistry |
title | Design, development, and characterization of an idebenone-loaded poly-ε-caprolactone intravitreal implant as a new therapeutic approach for LHON treatment |
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