Dual Delivery of Cyclosporin A and Etodolac Using Polymeric Nanocapsules in a Rabbit Eye Model: Ocular Biodistribution and Pharmacokinetic Study
Commercially available eye drops are loaded only with a single drug. By using the polymeric nanocapsules, dual delivery of 0.05% w/w cyclosporin A (CsA) and 0.2% w/w etodolac (Edc) was achieved. An ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for...
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| Veröffentlicht in: | Journal of ocular pharmacology and therapeutics 2022-12, Vol.38 (10), p.734-744 |
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| container_title | Journal of ocular pharmacology and therapeutics |
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| creator | Rahman, Syed Nazrin Ruhina Goswami, Abhinab Sree, Amoolya Jala, Aishwarya Borkar, Roshan M Shunmugaperumal, Tamilvanan |
| description | Commercially available eye drops are loaded only with a single drug. By using the polymeric nanocapsules, dual delivery of 0.05% w/w cyclosporin A (CsA) and 0.2% w/w etodolac (Edc) was achieved. An ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for determining simultaneously the biodistribution and pharmacokinetic profile of CsA and Edc in ocular tissues.
After one single drop instillation of nanocapsules into healthy right eyes of rabbits, the eyeballs were enucleated at 5, 15, 30, 60, and 90 min time periods to separate the 5 different ocular tissues. A liquid/liquid extraction method was used for ocular sample extraction using darunavir as internal standard. Using 3 diverse conditions such as bench-top, autosampler, and freeze-thaw, the stability of the analytes at 3 quality control samples in ocular tissues was also checked.
Intra- and interday precisions for both CsA and Edc in multiple ocular tissues were |
| doi_str_mv | 10.1089/jop.2022.0092 |
| format | Article |
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After one single drop instillation of nanocapsules into healthy right eyes of rabbits, the eyeballs were enucleated at 5, 15, 30, 60, and 90 min time periods to separate the 5 different ocular tissues. A liquid/liquid extraction method was used for ocular sample extraction using darunavir as internal standard. Using 3 diverse conditions such as bench-top, autosampler, and freeze-thaw, the stability of the analytes at 3 quality control samples in ocular tissues was also checked.
Intra- and interday precisions for both CsA and Edc in multiple ocular tissues were <10.32%, and the accuracy was <11.98%. The % bias and % RSD values for CsA and Edc were found within the acceptable limit of ±15%. The highest C
values were attained in cornea for both the drugs at 60 min postinstillation time point. Despite molecular size and structural differences, both CsA and Edc after liberation from nanocapsule drops can permeate into the tissues of the anterior as well as posterior segments of the eye.
The biodistribution and pharmacokinetic data might help and strengthen our understanding of synergetic anti-inflammatory activity of CsA and Edc from nanocapsules after its ocular topical application for managing keratoconjunctivitis sicca.</description><identifier>ISSN: 1080-7683</identifier><identifier>EISSN: 1557-7732</identifier><identifier>DOI: 10.1089/jop.2022.0092</identifier><identifier>PMID: 36355052</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Chromatography, Liquid ; Cyclosporine ; Etodolac ; Nanocapsules ; Rabbits ; Tandem Mass Spectrometry ; Tissue Distribution</subject><ispartof>Journal of ocular pharmacology and therapeutics, 2022-12, Vol.38 (10), p.734-744</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c223t-49b6e355049f530b2f8d5b03241469e37d1699862bbe5cc12b3306d6ae308903</citedby><cites>FETCH-LOGICAL-c223t-49b6e355049f530b2f8d5b03241469e37d1699862bbe5cc12b3306d6ae308903</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/36355052$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rahman, Syed Nazrin Ruhina</creatorcontrib><creatorcontrib>Goswami, Abhinab</creatorcontrib><creatorcontrib>Sree, Amoolya</creatorcontrib><creatorcontrib>Jala, Aishwarya</creatorcontrib><creatorcontrib>Borkar, Roshan M</creatorcontrib><creatorcontrib>Shunmugaperumal, Tamilvanan</creatorcontrib><title>Dual Delivery of Cyclosporin A and Etodolac Using Polymeric Nanocapsules in a Rabbit Eye Model: Ocular Biodistribution and Pharmacokinetic Study</title><title>Journal of ocular pharmacology and therapeutics</title><addtitle>J Ocul Pharmacol Ther</addtitle><description>Commercially available eye drops are loaded only with a single drug. By using the polymeric nanocapsules, dual delivery of 0.05% w/w cyclosporin A (CsA) and 0.2% w/w etodolac (Edc) was achieved. An ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for determining simultaneously the biodistribution and pharmacokinetic profile of CsA and Edc in ocular tissues.
After one single drop instillation of nanocapsules into healthy right eyes of rabbits, the eyeballs were enucleated at 5, 15, 30, 60, and 90 min time periods to separate the 5 different ocular tissues. A liquid/liquid extraction method was used for ocular sample extraction using darunavir as internal standard. Using 3 diverse conditions such as bench-top, autosampler, and freeze-thaw, the stability of the analytes at 3 quality control samples in ocular tissues was also checked.
Intra- and interday precisions for both CsA and Edc in multiple ocular tissues were <10.32%, and the accuracy was <11.98%. The % bias and % RSD values for CsA and Edc were found within the acceptable limit of ±15%. The highest C
values were attained in cornea for both the drugs at 60 min postinstillation time point. Despite molecular size and structural differences, both CsA and Edc after liberation from nanocapsule drops can permeate into the tissues of the anterior as well as posterior segments of the eye.
The biodistribution and pharmacokinetic data might help and strengthen our understanding of synergetic anti-inflammatory activity of CsA and Edc from nanocapsules after its ocular topical application for managing keratoconjunctivitis sicca.</description><subject>Animals</subject><subject>Chromatography, Liquid</subject><subject>Cyclosporine</subject><subject>Etodolac</subject><subject>Nanocapsules</subject><subject>Rabbits</subject><subject>Tandem Mass Spectrometry</subject><subject>Tissue Distribution</subject><issn>1080-7683</issn><issn>1557-7732</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kcdOxDAURS0Eogws2SIv2WRwGaewg5mhSDRR1pHLCxicONgJUv6CTyZDW723ODrSvRehfUqmlOTF0atvp4wwNiWkYGtomwqRJVnG2fr4k5wkWZrzLbQT4yshlJOUbqItnnIhiGDb6HPRS4cX4OwHhAH7Cs8H7XxsfbANPsGyMXjZeeOd1Pgp2uYZ33k31BCsxjey8Vq2sXcQ8YhLfC-Vsh1eDoCvvQF3jG9172TAp9YbG7tgVd9Z33x7715kqKX2b7aBbtQ9dL0ZdtFGJV2Evd87QY9ny8f5RXJ1e345P7lKNGO8S2aFSmEVYlZUghPFqtwIRTib0VlaAM8MTYsiT5lSILSmTPExu0kl8LE1wifo8EfbBv_eQ-zK2kYNzskGfB9LlnFBM8LGpiYo-UF18DEGqMo22FqGoaSkXG1QjhuUqw3K1QYjf_Cr7lUN5p_-K51_AcRMgtY</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Rahman, Syed Nazrin Ruhina</creator><creator>Goswami, Abhinab</creator><creator>Sree, Amoolya</creator><creator>Jala, Aishwarya</creator><creator>Borkar, Roshan M</creator><creator>Shunmugaperumal, Tamilvanan</creator><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>202212</creationdate><title>Dual Delivery of Cyclosporin A and Etodolac Using Polymeric Nanocapsules in a Rabbit Eye Model: Ocular Biodistribution and Pharmacokinetic Study</title><author>Rahman, Syed Nazrin Ruhina ; Goswami, Abhinab ; Sree, Amoolya ; Jala, Aishwarya ; Borkar, Roshan M ; Shunmugaperumal, Tamilvanan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c223t-49b6e355049f530b2f8d5b03241469e37d1699862bbe5cc12b3306d6ae308903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Chromatography, Liquid</topic><topic>Cyclosporine</topic><topic>Etodolac</topic><topic>Nanocapsules</topic><topic>Rabbits</topic><topic>Tandem Mass Spectrometry</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rahman, Syed Nazrin Ruhina</creatorcontrib><creatorcontrib>Goswami, Abhinab</creatorcontrib><creatorcontrib>Sree, Amoolya</creatorcontrib><creatorcontrib>Jala, Aishwarya</creatorcontrib><creatorcontrib>Borkar, Roshan M</creatorcontrib><creatorcontrib>Shunmugaperumal, Tamilvanan</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>Journal of ocular pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rahman, Syed Nazrin Ruhina</au><au>Goswami, Abhinab</au><au>Sree, Amoolya</au><au>Jala, Aishwarya</au><au>Borkar, Roshan M</au><au>Shunmugaperumal, Tamilvanan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dual Delivery of Cyclosporin A and Etodolac Using Polymeric Nanocapsules in a Rabbit Eye Model: Ocular Biodistribution and Pharmacokinetic Study</atitle><jtitle>Journal of ocular pharmacology and therapeutics</jtitle><addtitle>J Ocul Pharmacol Ther</addtitle><date>2022-12</date><risdate>2022</risdate><volume>38</volume><issue>10</issue><spage>734</spage><epage>744</epage><pages>734-744</pages><issn>1080-7683</issn><eissn>1557-7732</eissn><abstract>Commercially available eye drops are loaded only with a single drug. By using the polymeric nanocapsules, dual delivery of 0.05% w/w cyclosporin A (CsA) and 0.2% w/w etodolac (Edc) was achieved. An ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for determining simultaneously the biodistribution and pharmacokinetic profile of CsA and Edc in ocular tissues.
After one single drop instillation of nanocapsules into healthy right eyes of rabbits, the eyeballs were enucleated at 5, 15, 30, 60, and 90 min time periods to separate the 5 different ocular tissues. A liquid/liquid extraction method was used for ocular sample extraction using darunavir as internal standard. Using 3 diverse conditions such as bench-top, autosampler, and freeze-thaw, the stability of the analytes at 3 quality control samples in ocular tissues was also checked.
Intra- and interday precisions for both CsA and Edc in multiple ocular tissues were <10.32%, and the accuracy was <11.98%. The % bias and % RSD values for CsA and Edc were found within the acceptable limit of ±15%. The highest C
values were attained in cornea for both the drugs at 60 min postinstillation time point. Despite molecular size and structural differences, both CsA and Edc after liberation from nanocapsule drops can permeate into the tissues of the anterior as well as posterior segments of the eye.
The biodistribution and pharmacokinetic data might help and strengthen our understanding of synergetic anti-inflammatory activity of CsA and Edc from nanocapsules after its ocular topical application for managing keratoconjunctivitis sicca.</abstract><cop>United States</cop><pmid>36355052</pmid><doi>10.1089/jop.2022.0092</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals Chromatography, Liquid Cyclosporine Etodolac Nanocapsules Rabbits Tandem Mass Spectrometry Tissue Distribution |
| title | Dual Delivery of Cyclosporin A and Etodolac Using Polymeric Nanocapsules in a Rabbit Eye Model: Ocular Biodistribution and Pharmacokinetic Study |
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