Co-delivery of metformin and levofloxacin hydrochloride using biodegradable thermosensitive hydrogel for the treatment of corneal neovascularization
Corneal neovascularization (CNV) is one of the major causes of severe disorders in ocular surface. Subconjunctival administration provides a localized and effective delivery of anti-angiogenic agents to inhibit neovascularization. In the present study, the ABA triblock copolymer of poly(D,L-lactic-c...
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| Veröffentlicht in: | Drug delivery 2019-01, Vol.26 (1), p.522-531 |
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| creator | Liu, Dong Wu, Qianni Zhu, Yuqiong Liu, Yijun Xie, Xiuli Li, Sihan Lin, Haotian Chen, Weirong Zhu, Fangming |
| description | Corneal neovascularization (CNV) is one of the major causes of severe disorders in ocular surface. Subconjunctival administration provides a localized and effective delivery of anti-angiogenic agents to inhibit neovascularization. In the present study, the ABA triblock copolymer of poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) was used as a sustained drug delivery carrier for metformin (MET) and levofloxacin hydrochloride (LFH). Both drugs and PLGA-PEG-PLGA copolymers could be easily dissolved in water at low or room temperature and the mixed solution could form a drug-loaded thermosensitive hydrogel in terms of body temperature response. The in vitro release investigation displayed a sustained release of MET and LFH from the formulation for one month. The in vivo efficacy of subconjunctival injection of the MET + LFH loaded thermosensitive hydrogel in inhibiting CNV was evaluated on a mouse model of corneal alkali burn. Compared with the single administration of MET or LFH loaded thermosensitive hydrogel, the MET + LFH loaded thermosensitive hydrogel remarkably inhibited the formation of CNV. The sustained release of MET and an antibiotic (LFH) provides synergistic therapeutic outcome. As a result, the co-delivery of MET and LFH using PLGA-PEG-PLGA thermosensitive hydrogel by subconjunctival injection has great potential for ocular anti-angiogenic therapy. |
| doi_str_mv | 10.1080/10717544.2019.1609623 |
| format | Article |
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Subconjunctival administration provides a localized and effective delivery of anti-angiogenic agents to inhibit neovascularization. In the present study, the ABA triblock copolymer of poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) was used as a sustained drug delivery carrier for metformin (MET) and levofloxacin hydrochloride (LFH). Both drugs and PLGA-PEG-PLGA copolymers could be easily dissolved in water at low or room temperature and the mixed solution could form a drug-loaded thermosensitive hydrogel in terms of body temperature response. The in vitro release investigation displayed a sustained release of MET and LFH from the formulation for one month. The in vivo efficacy of subconjunctival injection of the MET + LFH loaded thermosensitive hydrogel in inhibiting CNV was evaluated on a mouse model of corneal alkali burn. Compared with the single administration of MET or LFH loaded thermosensitive hydrogel, the MET + LFH loaded thermosensitive hydrogel remarkably inhibited the formation of CNV. The sustained release of MET and an antibiotic (LFH) provides synergistic therapeutic outcome. As a result, the co-delivery of MET and LFH using PLGA-PEG-PLGA thermosensitive hydrogel by subconjunctival injection has great potential for ocular anti-angiogenic therapy.</description><identifier>ISSN: 1071-7544</identifier><identifier>EISSN: 1521-0464</identifier><identifier>DOI: 10.1080/10717544.2019.1609623</identifier><identifier>PMID: 31090470</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Acids ; Angiogenesis ; Antibiotics ; Antidiabetics ; Biodegradation ; Cornea ; corneal neovascularization ; Cytokines ; Drug delivery systems ; Drugs ; Hydrogels ; Kinases ; metformin ; Polymers ; subconjunctival injection ; synergistic effect ; Thermosensitive hydrogel ; Vascular endothelial growth factor</subject><ispartof>Drug delivery, 2019-01, Vol.26 (1), p.522-531</ispartof><rights>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2019</rights><rights>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/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>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2019 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c628t-ae8076791159586ec6cf950768d01bbdd1e9fc284ccdc9440bbeb155c3c925973</citedby><cites>FETCH-LOGICAL-c628t-ae8076791159586ec6cf950768d01bbdd1e9fc284ccdc9440bbeb155c3c925973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534255/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534255/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,27481,27903,27904,53769,53771,59119,59120</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31090470$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Dong</creatorcontrib><creatorcontrib>Wu, Qianni</creatorcontrib><creatorcontrib>Zhu, Yuqiong</creatorcontrib><creatorcontrib>Liu, Yijun</creatorcontrib><creatorcontrib>Xie, Xiuli</creatorcontrib><creatorcontrib>Li, Sihan</creatorcontrib><creatorcontrib>Lin, Haotian</creatorcontrib><creatorcontrib>Chen, Weirong</creatorcontrib><creatorcontrib>Zhu, Fangming</creatorcontrib><title>Co-delivery of metformin and levofloxacin hydrochloride using biodegradable thermosensitive hydrogel for the treatment of corneal neovascularization</title><title>Drug delivery</title><addtitle>Drug Deliv</addtitle><description>Corneal neovascularization (CNV) is one of the major causes of severe disorders in ocular surface. Subconjunctival administration provides a localized and effective delivery of anti-angiogenic agents to inhibit neovascularization. In the present study, the ABA triblock copolymer of poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) was used as a sustained drug delivery carrier for metformin (MET) and levofloxacin hydrochloride (LFH). Both drugs and PLGA-PEG-PLGA copolymers could be easily dissolved in water at low or room temperature and the mixed solution could form a drug-loaded thermosensitive hydrogel in terms of body temperature response. The in vitro release investigation displayed a sustained release of MET and LFH from the formulation for one month. The in vivo efficacy of subconjunctival injection of the MET + LFH loaded thermosensitive hydrogel in inhibiting CNV was evaluated on a mouse model of corneal alkali burn. Compared with the single administration of MET or LFH loaded thermosensitive hydrogel, the MET + LFH loaded thermosensitive hydrogel remarkably inhibited the formation of CNV. The sustained release of MET and an antibiotic (LFH) provides synergistic therapeutic outcome. As a result, the co-delivery of MET and LFH using PLGA-PEG-PLGA thermosensitive hydrogel by subconjunctival injection has great potential for ocular anti-angiogenic therapy.</description><subject>Acids</subject><subject>Angiogenesis</subject><subject>Antibiotics</subject><subject>Antidiabetics</subject><subject>Biodegradation</subject><subject>Cornea</subject><subject>corneal neovascularization</subject><subject>Cytokines</subject><subject>Drug delivery systems</subject><subject>Drugs</subject><subject>Hydrogels</subject><subject>Kinases</subject><subject>metformin</subject><subject>Polymers</subject><subject>subconjunctival injection</subject><subject>synergistic effect</subject><subject>Thermosensitive hydrogel</subject><subject>Vascular endothelial growth factor</subject><issn>1071-7544</issn><issn>1521-0464</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks-O0zAQxiMEYpeFRwBF4pxiO7YTXxCo4s9KK3GBszWxJ60rx14ct1CegwfGod0Ve-Fka-ab3-eRv6p6ScmKkp68oaSjneB8xQhVKyqJkqx9VF1SwWhDuOSPy71omkV0UT2b5x0hpKdMPK0uWkoU4R25rH6vY2PRuwOmYx3HesI8xjS5UEOwtcdDHH38CaYUtkebotn6mJzFej-7sKkHFy1uElgYPNZ5i2mKM4bZ5UI8TWzQ1wW5NOucEPKEIS9WJqaA4OuA8QCz2XtI7hdkF8Pz6skIfsYX5_Oq-vbxw9f15-bmy6fr9fubxkjW5wawJ53sFKVCiV6ikWZUopR6S-gwWEtRjYb13BhrFOdkGHCgQpjWKCZU115V1yeujbDTt8lNkI46gtN_CzFtNKTsjEdtRxgkbbmkveQClOqURd6ZtmPQKWYL6-2JdbsfJrSmLJnAP4A-7AS31Zt40FK0nAlRAK_PgBS_73HOehf3KZT9NWsFJZxy0heVOKlMivOccLx3oEQvwdB3wdBLMPQ5GGXu1b_Pu5-6S0IRvDsJXFgCAD9i8lZnOJb_HhME4-ZF_D-PP62FzIs</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Liu, Dong</creator><creator>Wu, Qianni</creator><creator>Zhu, Yuqiong</creator><creator>Liu, Yijun</creator><creator>Xie, Xiuli</creator><creator>Li, Sihan</creator><creator>Lin, Haotian</creator><creator>Chen, Weirong</creator><creator>Zhu, Fangming</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><general>Taylor & Francis Group</general><scope>0YH</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>5PM</scope><scope>DOA</scope></search><sort><creationdate>20190101</creationdate><title>Co-delivery of metformin and levofloxacin hydrochloride using biodegradable thermosensitive hydrogel for the treatment of corneal neovascularization</title><author>Liu, Dong ; Wu, Qianni ; Zhu, Yuqiong ; Liu, Yijun ; Xie, Xiuli ; Li, Sihan ; Lin, Haotian ; Chen, Weirong ; Zhu, Fangming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c628t-ae8076791159586ec6cf950768d01bbdd1e9fc284ccdc9440bbeb155c3c925973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acids</topic><topic>Angiogenesis</topic><topic>Antibiotics</topic><topic>Antidiabetics</topic><topic>Biodegradation</topic><topic>Cornea</topic><topic>corneal neovascularization</topic><topic>Cytokines</topic><topic>Drug delivery systems</topic><topic>Drugs</topic><topic>Hydrogels</topic><topic>Kinases</topic><topic>metformin</topic><topic>Polymers</topic><topic>subconjunctival injection</topic><topic>synergistic effect</topic><topic>Thermosensitive hydrogel</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Dong</creatorcontrib><creatorcontrib>Wu, Qianni</creatorcontrib><creatorcontrib>Zhu, Yuqiong</creatorcontrib><creatorcontrib>Liu, Yijun</creatorcontrib><creatorcontrib>Xie, Xiuli</creatorcontrib><creatorcontrib>Li, Sihan</creatorcontrib><creatorcontrib>Lin, Haotian</creatorcontrib><creatorcontrib>Chen, Weirong</creatorcontrib><creatorcontrib>Zhu, Fangming</creatorcontrib><collection>Taylor & Francis Open Access</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>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>Liu, Dong</au><au>Wu, Qianni</au><au>Zhu, Yuqiong</au><au>Liu, Yijun</au><au>Xie, Xiuli</au><au>Li, Sihan</au><au>Lin, Haotian</au><au>Chen, Weirong</au><au>Zhu, Fangming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Co-delivery of metformin and levofloxacin hydrochloride using biodegradable thermosensitive hydrogel for the treatment of corneal neovascularization</atitle><jtitle>Drug delivery</jtitle><addtitle>Drug Deliv</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>26</volume><issue>1</issue><spage>522</spage><epage>531</epage><pages>522-531</pages><issn>1071-7544</issn><eissn>1521-0464</eissn><abstract>Corneal neovascularization (CNV) is one of the major causes of severe disorders in ocular surface. Subconjunctival administration provides a localized and effective delivery of anti-angiogenic agents to inhibit neovascularization. In the present study, the ABA triblock copolymer of poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) was used as a sustained drug delivery carrier for metformin (MET) and levofloxacin hydrochloride (LFH). Both drugs and PLGA-PEG-PLGA copolymers could be easily dissolved in water at low or room temperature and the mixed solution could form a drug-loaded thermosensitive hydrogel in terms of body temperature response. The in vitro release investigation displayed a sustained release of MET and LFH from the formulation for one month. The in vivo efficacy of subconjunctival injection of the MET + LFH loaded thermosensitive hydrogel in inhibiting CNV was evaluated on a mouse model of corneal alkali burn. Compared with the single administration of MET or LFH loaded thermosensitive hydrogel, the MET + LFH loaded thermosensitive hydrogel remarkably inhibited the formation of CNV. The sustained release of MET and an antibiotic (LFH) provides synergistic therapeutic outcome. As a result, the co-delivery of MET and LFH using PLGA-PEG-PLGA thermosensitive hydrogel by subconjunctival injection has great potential for ocular anti-angiogenic therapy.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>31090470</pmid><doi>10.1080/10717544.2019.1609623</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Taylor & Francis Open Access; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Acids Angiogenesis Antibiotics Antidiabetics Biodegradation Cornea corneal neovascularization Cytokines Drug delivery systems Drugs Hydrogels Kinases metformin Polymers subconjunctival injection synergistic effect Thermosensitive hydrogel Vascular endothelial growth factor |
| title | Co-delivery of metformin and levofloxacin hydrochloride using biodegradable thermosensitive hydrogel for the treatment of corneal neovascularization |
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