Thermosensitive glycol chitosan-based hydrogel as a topical ocular drug delivery system for enhanced ocular bioavailability
[Display omitted] In the present study, we developed and evaluated an in situ gelling system based on hexanoyl glycol chitosan (H-GCS) for enhanced ocular bioavailability. An aqueous solution of H-GCS exhibited a typical sol-gel transition at 32 °C. The formed H-GCS hydrogel was characterized by rhe...
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| Veröffentlicht in: | International journal of pharmaceutics 2019-10, Vol.570, p.118688-118688, Article 118688 |
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| container_title | International journal of pharmaceutics |
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| creator | Shi, Hui Wang, Yuan Bao, Zhishu Lin, Deqing Liu, Hui Yu, Ailing Lei, Lei Li, Xingyi Xu, Xu |
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In the present study, we developed and evaluated an in situ gelling system based on hexanoyl glycol chitosan (H-GCS) for enhanced ocular bioavailability. An aqueous solution of H-GCS exhibited a typical sol-gel transition at 32 °C. The formed H-GCS hydrogel was characterized by rheology and scanning electron microscopy (SEM). H-GCS had minimal in vitro cytotoxicity against L-929 and HCEC cells over a concentration range of 0–0.8 mg/mL. Additionally, the H-GCS hydrogel exhibited good ocular tolerance and biocompatibility after a single instillation. Moreover, H-GCS hydrogel significantly prolonged the precorneal retention of fluorescein sodium compared with its aqueous solution. An in vivo pharmacokinetic study demonstrated that the levofloxacin-loaded H-GCS hydrogel could provide a significantly higher Cmax and AUC0-12h compared with the levofloxacin aqueous solution, thus increasing ocular bioavailability. Overall, the proposed H-GCS hydrogel acts as an in situ gelling system that might represent a promising vehicle for topical ocular drug delivery. |
| doi_str_mv | 10.1016/j.ijpharm.2019.118688 |
| format | Article |
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In the present study, we developed and evaluated an in situ gelling system based on hexanoyl glycol chitosan (H-GCS) for enhanced ocular bioavailability. An aqueous solution of H-GCS exhibited a typical sol-gel transition at 32 °C. The formed H-GCS hydrogel was characterized by rheology and scanning electron microscopy (SEM). H-GCS had minimal in vitro cytotoxicity against L-929 and HCEC cells over a concentration range of 0–0.8 mg/mL. Additionally, the H-GCS hydrogel exhibited good ocular tolerance and biocompatibility after a single instillation. Moreover, H-GCS hydrogel significantly prolonged the precorneal retention of fluorescein sodium compared with its aqueous solution. An in vivo pharmacokinetic study demonstrated that the levofloxacin-loaded H-GCS hydrogel could provide a significantly higher Cmax and AUC0-12h compared with the levofloxacin aqueous solution, thus increasing ocular bioavailability. Overall, the proposed H-GCS hydrogel acts as an in situ gelling system that might represent a promising vehicle for topical ocular drug delivery.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2019.118688</identifier><identifier>PMID: 31513870</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Biological Availability ; Cell Line ; Chitosan - chemistry ; Drug Delivery Systems - methods ; Drug Liberation - drug effects ; Eye - drug effects ; Eye - metabolism ; Humans ; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry ; Hydrogel, Polyethylene Glycol Dimethacrylate - metabolism ; In situ gelling system ; Levofloxacin - chemistry ; Levofloxacin - metabolism ; Ocular irritation ; Ophthalmic drug delivery ; Ophthalmic Solutions - chemistry ; Ophthalmic Solutions - metabolism ; Rabbits ; Temperature ; Thermosensitive hydrogel</subject><ispartof>International journal of pharmaceutics, 2019-10, Vol.570, p.118688-118688, Article 118688</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-43676625958fb8d23e8129d71e90379d9583f25cbd41300b0c43dba9baafd6383</citedby><cites>FETCH-LOGICAL-c365t-43676625958fb8d23e8129d71e90379d9583f25cbd41300b0c43dba9baafd6383</cites><orcidid>0000-0002-0368-4538</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378517319307331$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31513870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shi, Hui</creatorcontrib><creatorcontrib>Wang, Yuan</creatorcontrib><creatorcontrib>Bao, Zhishu</creatorcontrib><creatorcontrib>Lin, Deqing</creatorcontrib><creatorcontrib>Liu, Hui</creatorcontrib><creatorcontrib>Yu, Ailing</creatorcontrib><creatorcontrib>Lei, Lei</creatorcontrib><creatorcontrib>Li, Xingyi</creatorcontrib><creatorcontrib>Xu, Xu</creatorcontrib><title>Thermosensitive glycol chitosan-based hydrogel as a topical ocular drug delivery system for enhanced ocular bioavailability</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
In the present study, we developed and evaluated an in situ gelling system based on hexanoyl glycol chitosan (H-GCS) for enhanced ocular bioavailability. An aqueous solution of H-GCS exhibited a typical sol-gel transition at 32 °C. The formed H-GCS hydrogel was characterized by rheology and scanning electron microscopy (SEM). H-GCS had minimal in vitro cytotoxicity against L-929 and HCEC cells over a concentration range of 0–0.8 mg/mL. Additionally, the H-GCS hydrogel exhibited good ocular tolerance and biocompatibility after a single instillation. Moreover, H-GCS hydrogel significantly prolonged the precorneal retention of fluorescein sodium compared with its aqueous solution. An in vivo pharmacokinetic study demonstrated that the levofloxacin-loaded H-GCS hydrogel could provide a significantly higher Cmax and AUC0-12h compared with the levofloxacin aqueous solution, thus increasing ocular bioavailability. Overall, the proposed H-GCS hydrogel acts as an in situ gelling system that might represent a promising vehicle for topical ocular drug delivery.</description><subject>Animals</subject><subject>Biological Availability</subject><subject>Cell Line</subject><subject>Chitosan - chemistry</subject><subject>Drug Delivery Systems - methods</subject><subject>Drug Liberation - drug effects</subject><subject>Eye - drug effects</subject><subject>Eye - metabolism</subject><subject>Humans</subject><subject>Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry</subject><subject>Hydrogel, Polyethylene Glycol Dimethacrylate - metabolism</subject><subject>In situ gelling system</subject><subject>Levofloxacin - chemistry</subject><subject>Levofloxacin - metabolism</subject><subject>Ocular irritation</subject><subject>Ophthalmic drug delivery</subject><subject>Ophthalmic Solutions - chemistry</subject><subject>Ophthalmic Solutions - metabolism</subject><subject>Rabbits</subject><subject>Temperature</subject><subject>Thermosensitive hydrogel</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1r3DAQhkVJaLZpf0KLjrl4q4-1LJ1CCElaCPSSnoU-xmstsrWV7AXTPx8vu8k1p4HheedlHoS-U7KmhIqfu3XY7TuT-zUjVK0plULKT2hFZcMrvmnEBVoR3siqpg2_Ql9K2RFCBKP8M7ritKZcNmSF_r90kPtUYChhDAfA2zi7FLHrwpiKGSprCnjczT6nLURsCjZ4TPvgTMTJTdFk7PO0xR7iEs8zLnMZocdtyhiGzgxuiZ9BG5I5mBCNDTGM81d02ZpY4Nt5XqO_jw8v97-q5z9Pv-_vnivHRT1WGy4aIVitatla6RkHSZnyDQW1PKj8suctq531G8oJscRtuLdGWWNaL7jk1-jmdHef078Jyqj7UBzEaAZIU9GMKSKVoowvaH1CXU6lZGj1Pofe5FlToo_e9U6fveujd33yvuR-nCsm24N_T72JXoDbEwDLo4cAWRcX4CgnZHCj9il8UPEKeNWZIQ</recordid><startdate>20191030</startdate><enddate>20191030</enddate><creator>Shi, Hui</creator><creator>Wang, Yuan</creator><creator>Bao, Zhishu</creator><creator>Lin, Deqing</creator><creator>Liu, Hui</creator><creator>Yu, Ailing</creator><creator>Lei, Lei</creator><creator>Li, Xingyi</creator><creator>Xu, Xu</creator><general>Elsevier B.V</general><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><orcidid>https://orcid.org/0000-0002-0368-4538</orcidid></search><sort><creationdate>20191030</creationdate><title>Thermosensitive glycol chitosan-based hydrogel as a topical ocular drug delivery system for enhanced ocular bioavailability</title><author>Shi, Hui ; Wang, Yuan ; Bao, Zhishu ; Lin, Deqing ; Liu, Hui ; Yu, Ailing ; Lei, Lei ; Li, Xingyi ; Xu, Xu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-43676625958fb8d23e8129d71e90379d9583f25cbd41300b0c43dba9baafd6383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Biological Availability</topic><topic>Cell Line</topic><topic>Chitosan - chemistry</topic><topic>Drug Delivery Systems - methods</topic><topic>Drug Liberation - drug effects</topic><topic>Eye - drug effects</topic><topic>Eye - metabolism</topic><topic>Humans</topic><topic>Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry</topic><topic>Hydrogel, Polyethylene Glycol Dimethacrylate - metabolism</topic><topic>In situ gelling system</topic><topic>Levofloxacin - chemistry</topic><topic>Levofloxacin - metabolism</topic><topic>Ocular irritation</topic><topic>Ophthalmic drug delivery</topic><topic>Ophthalmic Solutions - chemistry</topic><topic>Ophthalmic Solutions - metabolism</topic><topic>Rabbits</topic><topic>Temperature</topic><topic>Thermosensitive hydrogel</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shi, Hui</creatorcontrib><creatorcontrib>Wang, Yuan</creatorcontrib><creatorcontrib>Bao, Zhishu</creatorcontrib><creatorcontrib>Lin, Deqing</creatorcontrib><creatorcontrib>Liu, Hui</creatorcontrib><creatorcontrib>Yu, Ailing</creatorcontrib><creatorcontrib>Lei, Lei</creatorcontrib><creatorcontrib>Li, Xingyi</creatorcontrib><creatorcontrib>Xu, Xu</creatorcontrib><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>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shi, Hui</au><au>Wang, Yuan</au><au>Bao, Zhishu</au><au>Lin, Deqing</au><au>Liu, Hui</au><au>Yu, Ailing</au><au>Lei, Lei</au><au>Li, Xingyi</au><au>Xu, Xu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thermosensitive glycol chitosan-based hydrogel as a topical ocular drug delivery system for enhanced ocular bioavailability</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2019-10-30</date><risdate>2019</risdate><volume>570</volume><spage>118688</spage><epage>118688</epage><pages>118688-118688</pages><artnum>118688</artnum><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
In the present study, we developed and evaluated an in situ gelling system based on hexanoyl glycol chitosan (H-GCS) for enhanced ocular bioavailability. An aqueous solution of H-GCS exhibited a typical sol-gel transition at 32 °C. The formed H-GCS hydrogel was characterized by rheology and scanning electron microscopy (SEM). H-GCS had minimal in vitro cytotoxicity against L-929 and HCEC cells over a concentration range of 0–0.8 mg/mL. Additionally, the H-GCS hydrogel exhibited good ocular tolerance and biocompatibility after a single instillation. Moreover, H-GCS hydrogel significantly prolonged the precorneal retention of fluorescein sodium compared with its aqueous solution. An in vivo pharmacokinetic study demonstrated that the levofloxacin-loaded H-GCS hydrogel could provide a significantly higher Cmax and AUC0-12h compared with the levofloxacin aqueous solution, thus increasing ocular bioavailability. Overall, the proposed H-GCS hydrogel acts as an in situ gelling system that might represent a promising vehicle for topical ocular drug delivery.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31513870</pmid><doi>10.1016/j.ijpharm.2019.118688</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0368-4538</orcidid></addata></record> |
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| subjects | Animals Biological Availability Cell Line Chitosan - chemistry Drug Delivery Systems - methods Drug Liberation - drug effects Eye - drug effects Eye - metabolism Humans Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry Hydrogel, Polyethylene Glycol Dimethacrylate - metabolism In situ gelling system Levofloxacin - chemistry Levofloxacin - metabolism Ocular irritation Ophthalmic drug delivery Ophthalmic Solutions - chemistry Ophthalmic Solutions - metabolism Rabbits Temperature Thermosensitive hydrogel |
| title | Thermosensitive glycol chitosan-based hydrogel as a topical ocular drug delivery system for enhanced ocular bioavailability |
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