Chitosan Nanoparticles as a Potential Drug Delivery System for the Ocular Surface: Toxicity, Uptake Mechanism and In Vivo Tolerance
To study the in vitro and in vivo interaction of chitosan nanoparticles (CSNPs), a new particulate drug carrier, with epithelial cells on the ocular surface. CSNPs labeled with fluorescein isothiocyanate-bovine serum albumin were produced by ionotropic gelation. Human conjunctival epithelial cells (...
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| Veröffentlicht in: | Investigative ophthalmology & visual science 2006-04, Vol.47 (4), p.1416-1425 |
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| creator | de Salamanca, Amalia Enriquez Diebold, Yolanda Calonge, Margarita Garcia-Vazquez, Carmen Callejo, Sagrario Vila, Ana Alonso, Maria Jose |
| description | To study the in vitro and in vivo interaction of chitosan nanoparticles (CSNPs), a new particulate drug carrier, with epithelial cells on the ocular surface.
CSNPs labeled with fluorescein isothiocyanate-bovine serum albumin were produced by ionotropic gelation. Human conjunctival epithelial cells (IOBA-NHC) were exposed for 15, 30, 60, and 120 minutes to three different CSNP concentrations. Immediately after treatment and after a 24-hour recovery period in culture medium, cell survival, and viability were measured. The association of CSNPs with IOBA-NHC cells was investigated by confocal microscopy. The influence of temperature and the effect of metabolic inhibition were studied by fluorometry. The in vivo uptake and acute tolerance of the ocular surface to CSNPs were evaluated in rabbits.
Cell survival and viability of CSNP-exposed cells were equivalent to that of the control. Uptake of CSNPs was continuous for the 2-hour duration of these experiments and was temperature dependent. Metabolic inhibition by sodium azide had no effect on CSNP uptake. The rabbit ocular surface showed no signs of inflammation or alteration after CSNP exposure compared with the control. Fluorescence microscopy of rabbit eyeball and lid sections confirmed in vivo uptake by conjunctival and corneal epithelia.
CSNPs were internalized by IOBA-NHC cells by an active transport mechanism that did not compromise cell viability. Moreover, these nanoparticles were well tolerated by the ocular surface tissues. These facts add further support for the potential use of these colloidal systems to delivery drugs to the ocular surface. |
| doi_str_mv | 10.1167/iovs.05-0495 |
| format | Article |
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CSNPs labeled with fluorescein isothiocyanate-bovine serum albumin were produced by ionotropic gelation. Human conjunctival epithelial cells (IOBA-NHC) were exposed for 15, 30, 60, and 120 minutes to three different CSNP concentrations. Immediately after treatment and after a 24-hour recovery period in culture medium, cell survival, and viability were measured. The association of CSNPs with IOBA-NHC cells was investigated by confocal microscopy. The influence of temperature and the effect of metabolic inhibition were studied by fluorometry. The in vivo uptake and acute tolerance of the ocular surface to CSNPs were evaluated in rabbits.
Cell survival and viability of CSNP-exposed cells were equivalent to that of the control. Uptake of CSNPs was continuous for the 2-hour duration of these experiments and was temperature dependent. Metabolic inhibition by sodium azide had no effect on CSNP uptake. The rabbit ocular surface showed no signs of inflammation or alteration after CSNP exposure compared with the control. Fluorescence microscopy of rabbit eyeball and lid sections confirmed in vivo uptake by conjunctival and corneal epithelia.
CSNPs were internalized by IOBA-NHC cells by an active transport mechanism that did not compromise cell viability. Moreover, these nanoparticles were well tolerated by the ocular surface tissues. These facts add further support for the potential use of these colloidal systems to delivery drugs to the ocular surface.</description><identifier>ISSN: 0146-0404</identifier><identifier>ISSN: 1552-5783</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.05-0495</identifier><identifier>PMID: 16565375</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Animals ; Biological and medical sciences ; Biological Transport ; Cell Count ; Cell Survival - drug effects ; Cells, Cultured ; Chitosan - pharmacokinetics ; Chitosan - toxicity ; Conjunctiva - drug effects ; Conjunctiva - metabolism ; Cornea - drug effects ; Cornea - metabolism ; Drug Carriers ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Eye and associated structures. Visual pathways and centers. Vision ; Female ; Fluorescein-5-isothiocyanate - analogs & derivatives ; Fluorescein-5-isothiocyanate - pharmacokinetics ; Fluorescein-5-isothiocyanate - toxicity ; Fluorophotometry ; Fundamental and applied biological sciences. Psychology ; Humans ; Microscopy, Confocal ; Microspheres ; Rabbits ; Serum Albumin, Bovine - pharmacokinetics ; Serum Albumin, Bovine - toxicity ; Vertebrates: nervous system and sense organs</subject><ispartof>Investigative ophthalmology & visual science, 2006-04, Vol.47 (4), p.1416-1425</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-678d48a3a48a89e14a2c2d172a091943dc38700f5d48f1e08ab86327954a3b153</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17674800$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16565375$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Salamanca, Amalia Enriquez</creatorcontrib><creatorcontrib>Diebold, Yolanda</creatorcontrib><creatorcontrib>Calonge, Margarita</creatorcontrib><creatorcontrib>Garcia-Vazquez, Carmen</creatorcontrib><creatorcontrib>Callejo, Sagrario</creatorcontrib><creatorcontrib>Vila, Ana</creatorcontrib><creatorcontrib>Alonso, Maria Jose</creatorcontrib><title>Chitosan Nanoparticles as a Potential Drug Delivery System for the Ocular Surface: Toxicity, Uptake Mechanism and In Vivo Tolerance</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>To study the in vitro and in vivo interaction of chitosan nanoparticles (CSNPs), a new particulate drug carrier, with epithelial cells on the ocular surface.
CSNPs labeled with fluorescein isothiocyanate-bovine serum albumin were produced by ionotropic gelation. Human conjunctival epithelial cells (IOBA-NHC) were exposed for 15, 30, 60, and 120 minutes to three different CSNP concentrations. Immediately after treatment and after a 24-hour recovery period in culture medium, cell survival, and viability were measured. The association of CSNPs with IOBA-NHC cells was investigated by confocal microscopy. The influence of temperature and the effect of metabolic inhibition were studied by fluorometry. The in vivo uptake and acute tolerance of the ocular surface to CSNPs were evaluated in rabbits.
Cell survival and viability of CSNP-exposed cells were equivalent to that of the control. Uptake of CSNPs was continuous for the 2-hour duration of these experiments and was temperature dependent. Metabolic inhibition by sodium azide had no effect on CSNP uptake. The rabbit ocular surface showed no signs of inflammation or alteration after CSNP exposure compared with the control. Fluorescence microscopy of rabbit eyeball and lid sections confirmed in vivo uptake by conjunctival and corneal epithelia.
CSNPs were internalized by IOBA-NHC cells by an active transport mechanism that did not compromise cell viability. Moreover, these nanoparticles were well tolerated by the ocular surface tissues. These facts add further support for the potential use of these colloidal systems to delivery drugs to the ocular surface.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Cell Count</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Chitosan - pharmacokinetics</subject><subject>Chitosan - toxicity</subject><subject>Conjunctiva - drug effects</subject><subject>Conjunctiva - metabolism</subject><subject>Cornea - drug effects</subject><subject>Cornea - metabolism</subject><subject>Drug Carriers</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Eye and associated structures. Visual pathways and centers. Vision</subject><subject>Female</subject><subject>Fluorescein-5-isothiocyanate - analogs & derivatives</subject><subject>Fluorescein-5-isothiocyanate - pharmacokinetics</subject><subject>Fluorescein-5-isothiocyanate - toxicity</subject><subject>Fluorophotometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Microscopy, Confocal</subject><subject>Microspheres</subject><subject>Rabbits</subject><subject>Serum Albumin, Bovine - pharmacokinetics</subject><subject>Serum Albumin, Bovine - toxicity</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0146-0404</issn><issn>1552-5783</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0E1rGzEQBmBRWhon6S3noktzyqbSSlppcwvORwNJU8jHVYy12qwa7a6RZDs-549HxobAMAPDw8C8CB1RckppJX-7cRlPiSgIr8UXNKFClIWQin1FE0J5lfeE76H9GP8TUlJaku9oj1aiEkyKCXqfdi6NEQb8F4ZxDiE5423EkAv_G5MdkgOPL8LiBV9Y75Y2rPHDOibb43YMOHUW35uFh4AfFqEFY8_w4_jmjEvrE_w0T_Bq8Z01HQwu9hiGBt8M-Nktx8y8DTAYe4i-teCj_bGbB-jp6vJx-qe4vb--mZ7fFoYplYpKqoYrYJCbqi3lUJqyobIEUtOasyYzSUgrsmqpJQpmqmKlrAUHNqOCHaCT7V0TxhiDbfU8uB7CWlOiN1nqTZaaCL3JMvOfWz5fzHrbfOJdeBn82gGIBny7ecbFTycryRUh2R1vXedeupULVscevM9nqV6tVlxqrimnFfsA-8-Kmw</recordid><startdate>20060401</startdate><enddate>20060401</enddate><creator>de Salamanca, Amalia Enriquez</creator><creator>Diebold, Yolanda</creator><creator>Calonge, Margarita</creator><creator>Garcia-Vazquez, Carmen</creator><creator>Callejo, Sagrario</creator><creator>Vila, Ana</creator><creator>Alonso, Maria Jose</creator><general>ARVO</general><general>Association for Research in Vision and Ophtalmology</general><scope>IQODW</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></search><sort><creationdate>20060401</creationdate><title>Chitosan Nanoparticles as a Potential Drug Delivery System for the Ocular Surface: Toxicity, Uptake Mechanism and In Vivo Tolerance</title><author>de Salamanca, Amalia Enriquez ; Diebold, Yolanda ; Calonge, Margarita ; Garcia-Vazquez, Carmen ; Callejo, Sagrario ; Vila, Ana ; Alonso, Maria Jose</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-678d48a3a48a89e14a2c2d172a091943dc38700f5d48f1e08ab86327954a3b153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biological Transport</topic><topic>Cell Count</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>Chitosan - pharmacokinetics</topic><topic>Chitosan - toxicity</topic><topic>Conjunctiva - drug effects</topic><topic>Conjunctiva - metabolism</topic><topic>Cornea - drug effects</topic><topic>Cornea - metabolism</topic><topic>Drug Carriers</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Eye and associated structures. Visual pathways and centers. Vision</topic><topic>Female</topic><topic>Fluorescein-5-isothiocyanate - analogs & derivatives</topic><topic>Fluorescein-5-isothiocyanate - pharmacokinetics</topic><topic>Fluorescein-5-isothiocyanate - toxicity</topic><topic>Fluorophotometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Microscopy, Confocal</topic><topic>Microspheres</topic><topic>Rabbits</topic><topic>Serum Albumin, Bovine - pharmacokinetics</topic><topic>Serum Albumin, Bovine - toxicity</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Salamanca, Amalia Enriquez</creatorcontrib><creatorcontrib>Diebold, Yolanda</creatorcontrib><creatorcontrib>Calonge, Margarita</creatorcontrib><creatorcontrib>Garcia-Vazquez, Carmen</creatorcontrib><creatorcontrib>Callejo, Sagrario</creatorcontrib><creatorcontrib>Vila, Ana</creatorcontrib><creatorcontrib>Alonso, Maria Jose</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Salamanca, Amalia Enriquez</au><au>Diebold, Yolanda</au><au>Calonge, Margarita</au><au>Garcia-Vazquez, Carmen</au><au>Callejo, Sagrario</au><au>Vila, Ana</au><au>Alonso, Maria Jose</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chitosan Nanoparticles as a Potential Drug Delivery System for the Ocular Surface: Toxicity, Uptake Mechanism and In Vivo Tolerance</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2006-04-01</date><risdate>2006</risdate><volume>47</volume><issue>4</issue><spage>1416</spage><epage>1425</epage><pages>1416-1425</pages><issn>0146-0404</issn><issn>1552-5783</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>To study the in vitro and in vivo interaction of chitosan nanoparticles (CSNPs), a new particulate drug carrier, with epithelial cells on the ocular surface.
CSNPs labeled with fluorescein isothiocyanate-bovine serum albumin were produced by ionotropic gelation. Human conjunctival epithelial cells (IOBA-NHC) were exposed for 15, 30, 60, and 120 minutes to three different CSNP concentrations. Immediately after treatment and after a 24-hour recovery period in culture medium, cell survival, and viability were measured. The association of CSNPs with IOBA-NHC cells was investigated by confocal microscopy. The influence of temperature and the effect of metabolic inhibition were studied by fluorometry. The in vivo uptake and acute tolerance of the ocular surface to CSNPs were evaluated in rabbits.
Cell survival and viability of CSNP-exposed cells were equivalent to that of the control. Uptake of CSNPs was continuous for the 2-hour duration of these experiments and was temperature dependent. Metabolic inhibition by sodium azide had no effect on CSNP uptake. The rabbit ocular surface showed no signs of inflammation or alteration after CSNP exposure compared with the control. Fluorescence microscopy of rabbit eyeball and lid sections confirmed in vivo uptake by conjunctival and corneal epithelia.
CSNPs were internalized by IOBA-NHC cells by an active transport mechanism that did not compromise cell viability. Moreover, these nanoparticles were well tolerated by the ocular surface tissues. These facts add further support for the potential use of these colloidal systems to delivery drugs to the ocular surface.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>16565375</pmid><doi>10.1167/iovs.05-0495</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0146-0404 |
| ispartof | Investigative ophthalmology & visual science, 2006-04, Vol.47 (4), p.1416-1425 |
| issn | 0146-0404 1552-5783 1552-5783 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Biological and medical sciences Biological Transport Cell Count Cell Survival - drug effects Cells, Cultured Chitosan - pharmacokinetics Chitosan - toxicity Conjunctiva - drug effects Conjunctiva - metabolism Cornea - drug effects Cornea - metabolism Drug Carriers Epithelial Cells - drug effects Epithelial Cells - metabolism Eye and associated structures. Visual pathways and centers. Vision Female Fluorescein-5-isothiocyanate - analogs & derivatives Fluorescein-5-isothiocyanate - pharmacokinetics Fluorescein-5-isothiocyanate - toxicity Fluorophotometry Fundamental and applied biological sciences. Psychology Humans Microscopy, Confocal Microspheres Rabbits Serum Albumin, Bovine - pharmacokinetics Serum Albumin, Bovine - toxicity Vertebrates: nervous system and sense organs |
| title | Chitosan Nanoparticles as a Potential Drug Delivery System for the Ocular Surface: Toxicity, Uptake Mechanism and In Vivo Tolerance |
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