Modulated release of cyclosporine from soluble vinyl pyrrolidone–hydroxyethyl methacrylate copolymer hydrogels: A correlation of ‘in vitro’ and ‘in vivo’ experiments
Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of the immunosuppressor cyclosporine. Two copolymeric systems with copolymer comp...
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| Veröffentlicht in: | Journal of controlled release 2001-05, Vol.72 (1), p.1-11 |
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| creator | Gallardo, Alberto Fernández, Fernando Cifuentes, Alejandro Dı́ez-Masa, José-Carlos Bermejo, Paloma Rebuelta, Mercedes López-Bravo, Antonio San Román, Julio |
| description | Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of the immunosuppressor cyclosporine. Two copolymeric systems with copolymer compositions
f
VP=0.52 (namely VP–HEMA 60–40) and 0.42 (VP–HEMA 40–60) have been prepared and tested in vitro and in vivo using rats as animal model. Micellar electrokinetic capillary chromatography, MEKC, has been used for the simultaneous detection of the polymer reabsorption and the drug release for the in vitro experiments. The composition and microstructural distribution of the copolymer system controls the solubilization rate which modulates the in vitro release of the drug (with time profiles from a few days to several weeks for the VP–HEMA 60–40 and 40–60, respectively) and the in vivo response that correlates with the previous in vitro results: the more hydrophobic implant (VP–HEMA 40–60) reverts the immune response more slowly (2–4 weeks) compared to the more hydrophilic one (VP–HEMA 60–40, 1–2 weeks). |
| doi_str_mv | 10.1016/S0168-3659(01)00257-7 |
| format | Article |
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f
VP=0.52 (namely VP–HEMA 60–40) and 0.42 (VP–HEMA 40–60) have been prepared and tested in vitro and in vivo using rats as animal model. Micellar electrokinetic capillary chromatography, MEKC, has been used for the simultaneous detection of the polymer reabsorption and the drug release for the in vitro experiments. The composition and microstructural distribution of the copolymer system controls the solubilization rate which modulates the in vitro release of the drug (with time profiles from a few days to several weeks for the VP–HEMA 60–40 and 40–60, respectively) and the in vivo response that correlates with the previous in vitro results: the more hydrophobic implant (VP–HEMA 40–60) reverts the immune response more slowly (2–4 weeks) compared to the more hydrophilic one (VP–HEMA 60–40, 1–2 weeks).</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/S0168-3659(01)00257-7</identifier><identifier>PMID: 11389980</identifier><identifier>CODEN: JCREEC</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>2-Hydroxyethyl methacrylate ; Animals ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Copolymers ; cyclosporin A ; Cyclosporine ; Cyclosporine - administration & dosage ; Cyclosporine - adverse effects ; Cyclosporine - pharmacokinetics ; Drug Carriers - chemistry ; Drug Compounding ; Drug Implants ; General pharmacology ; hydrogels ; Hydrogels - chemistry ; hydroxyethyl methacrylate ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - pharmacokinetics ; Male ; Medical sciences ; Methacrylates - chemistry ; Muscle, Skeletal - pathology ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Povidone - chemistry ; Rats ; Rats, Wistar ; Solubility ; vinyl pyrrolidone ; Vinylpyrrolidone</subject><ispartof>Journal of controlled release, 2001-05, Vol.72 (1), p.1-11</ispartof><rights>2001 Elsevier Science B.V.</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0168-3659(01)00257-7$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>309,310,314,780,784,789,790,3550,23930,23931,25140,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1043623$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11389980$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gallardo, Alberto</creatorcontrib><creatorcontrib>Fernández, Fernando</creatorcontrib><creatorcontrib>Cifuentes, Alejandro</creatorcontrib><creatorcontrib>Dı́ez-Masa, José-Carlos</creatorcontrib><creatorcontrib>Bermejo, Paloma</creatorcontrib><creatorcontrib>Rebuelta, Mercedes</creatorcontrib><creatorcontrib>López-Bravo, Antonio</creatorcontrib><creatorcontrib>San Román, Julio</creatorcontrib><title>Modulated release of cyclosporine from soluble vinyl pyrrolidone–hydroxyethyl methacrylate copolymer hydrogels: A correlation of ‘in vitro’ and ‘in vivo’ experiments</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of the immunosuppressor cyclosporine. Two copolymeric systems with copolymer compositions
f
VP=0.52 (namely VP–HEMA 60–40) and 0.42 (VP–HEMA 40–60) have been prepared and tested in vitro and in vivo using rats as animal model. Micellar electrokinetic capillary chromatography, MEKC, has been used for the simultaneous detection of the polymer reabsorption and the drug release for the in vitro experiments. The composition and microstructural distribution of the copolymer system controls the solubilization rate which modulates the in vitro release of the drug (with time profiles from a few days to several weeks for the VP–HEMA 60–40 and 40–60, respectively) and the in vivo response that correlates with the previous in vitro results: the more hydrophobic implant (VP–HEMA 40–60) reverts the immune response more slowly (2–4 weeks) compared to the more hydrophilic one (VP–HEMA 60–40, 1–2 weeks).</description><subject>2-Hydroxyethyl methacrylate</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Copolymers</subject><subject>cyclosporin A</subject><subject>Cyclosporine</subject><subject>Cyclosporine - administration & dosage</subject><subject>Cyclosporine - adverse effects</subject><subject>Cyclosporine - pharmacokinetics</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Compounding</subject><subject>Drug Implants</subject><subject>General pharmacology</subject><subject>hydrogels</subject><subject>Hydrogels - chemistry</subject><subject>hydroxyethyl methacrylate</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methacrylates - chemistry</subject><subject>Muscle, Skeletal - pathology</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Povidone - chemistry</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Solubility</subject><subject>vinyl pyrrolidone</subject><subject>Vinylpyrrolidone</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkU1uFDEQhS1ERIbAEUBeIASLBrvd7p9sUBRBQApiAawtt10mRm67sbtH6d3cgQ05BXeak8QzGcKmSnr16VWpHkLPKHlDCa3ffs2lLVjNu1eEviak5E3RPEAr2jasqLqOP0Sre-QYPU7pJyGEs6p5hI4pZW3XtWSF_n4OenZyAo0jOJAJcDBYLcqFNIZoPWATw4BTcHPvAK-tXxwelxiDszp42G5-Xy06husFpqs8GnKTKi47T6zCGNwyQMR75ge4dIrPshzzMjnZ4Hfbtps_1mfnKYbt5gZLr--l9V6B6xGiHcBP6Qk6MtIleHroJ-j7h_ffzj8Wl18uPp2fXRbASjYVvJK96XujG1ZpCaVpqOamhxKYlCWpSc0IrxUYJrmRbWV6wktW9x3XHaiGsxP08s53jOHXDGkSg00KnJMewpwEbTrCuppm8PkBnPsBtBjzoTIu4t-LM_DiAMikpDNRemXTf45UrC5Zxt7dYflHsLYQRVIWvAJtI6hJ6GAzK3bZi332YhesIFTssxcNuwUNjqr8</recordid><startdate>20010514</startdate><enddate>20010514</enddate><creator>Gallardo, Alberto</creator><creator>Fernández, Fernando</creator><creator>Cifuentes, Alejandro</creator><creator>Dı́ez-Masa, José-Carlos</creator><creator>Bermejo, Paloma</creator><creator>Rebuelta, Mercedes</creator><creator>López-Bravo, Antonio</creator><creator>San Román, Julio</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20010514</creationdate><title>Modulated release of cyclosporine from soluble vinyl pyrrolidone–hydroxyethyl methacrylate copolymer hydrogels: A correlation of ‘in vitro’ and ‘in vivo’ experiments</title><author>Gallardo, Alberto ; Fernández, Fernando ; Cifuentes, Alejandro ; Dı́ez-Masa, José-Carlos ; Bermejo, Paloma ; Rebuelta, Mercedes ; López-Bravo, Antonio ; San Román, Julio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e323t-54abfbbfd734dae2f71d5fbe2e3aa206063056cef3a5fa84fb05236b95d9ec753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>2-Hydroxyethyl methacrylate</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Copolymers</topic><topic>cyclosporin A</topic><topic>Cyclosporine</topic><topic>Cyclosporine - administration & dosage</topic><topic>Cyclosporine - adverse effects</topic><topic>Cyclosporine - pharmacokinetics</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Compounding</topic><topic>Drug Implants</topic><topic>General pharmacology</topic><topic>hydrogels</topic><topic>Hydrogels - chemistry</topic><topic>hydroxyethyl methacrylate</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methacrylates - chemistry</topic><topic>Muscle, Skeletal - pathology</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Povidone - chemistry</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Solubility</topic><topic>vinyl pyrrolidone</topic><topic>Vinylpyrrolidone</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gallardo, Alberto</creatorcontrib><creatorcontrib>Fernández, Fernando</creatorcontrib><creatorcontrib>Cifuentes, Alejandro</creatorcontrib><creatorcontrib>Dı́ez-Masa, José-Carlos</creatorcontrib><creatorcontrib>Bermejo, Paloma</creatorcontrib><creatorcontrib>Rebuelta, Mercedes</creatorcontrib><creatorcontrib>López-Bravo, Antonio</creatorcontrib><creatorcontrib>San Román, Julio</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>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gallardo, Alberto</au><au>Fernández, Fernando</au><au>Cifuentes, Alejandro</au><au>Dı́ez-Masa, José-Carlos</au><au>Bermejo, Paloma</au><au>Rebuelta, Mercedes</au><au>López-Bravo, Antonio</au><au>San Román, Julio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modulated release of cyclosporine from soluble vinyl pyrrolidone–hydroxyethyl methacrylate copolymer hydrogels: A correlation of ‘in vitro’ and ‘in vivo’ experiments</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2001-05-14</date><risdate>2001</risdate><volume>72</volume><issue>1</issue><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><coden>JCREEC</coden><abstract>Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of the immunosuppressor cyclosporine. Two copolymeric systems with copolymer compositions
f
VP=0.52 (namely VP–HEMA 60–40) and 0.42 (VP–HEMA 40–60) have been prepared and tested in vitro and in vivo using rats as animal model. Micellar electrokinetic capillary chromatography, MEKC, has been used for the simultaneous detection of the polymer reabsorption and the drug release for the in vitro experiments. The composition and microstructural distribution of the copolymer system controls the solubilization rate which modulates the in vitro release of the drug (with time profiles from a few days to several weeks for the VP–HEMA 60–40 and 40–60, respectively) and the in vivo response that correlates with the previous in vitro results: the more hydrophobic implant (VP–HEMA 40–60) reverts the immune response more slowly (2–4 weeks) compared to the more hydrophilic one (VP–HEMA 60–40, 1–2 weeks).</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>11389980</pmid><doi>10.1016/S0168-3659(01)00257-7</doi><tpages>11</tpages></addata></record> |
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| subjects | 2-Hydroxyethyl methacrylate Animals Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Copolymers cyclosporin A Cyclosporine Cyclosporine - administration & dosage Cyclosporine - adverse effects Cyclosporine - pharmacokinetics Drug Carriers - chemistry Drug Compounding Drug Implants General pharmacology hydrogels Hydrogels - chemistry hydroxyethyl methacrylate Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - pharmacokinetics Male Medical sciences Methacrylates - chemistry Muscle, Skeletal - pathology Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Povidone - chemistry Rats Rats, Wistar Solubility vinyl pyrrolidone Vinylpyrrolidone |
| title | Modulated release of cyclosporine from soluble vinyl pyrrolidone–hydroxyethyl methacrylate copolymer hydrogels: A correlation of ‘in vitro’ and ‘in vivo’ experiments |
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