Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis.
Identifieur interne : 003390 ( Main/Exploration ); précédent : 003389; suivant : 003391Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis.
Auteurs : RBID : pubmed:12707361English descriptors
- KwdEn :
- Albumins (pharmacokinetics), Animals, Arthritis, Experimental (drug therapy), Arthritis, Experimental (metabolism), Arthritis, Experimental (pathology), Arthritis, Rheumatoid (drug therapy), Arthritis, Rheumatoid (metabolism), Arthritis, Rheumatoid (pathology), Cells, Cultured, Drug Carriers (administration & dosage), Drug Carriers (pharmacokinetics), Drug Delivery Systems (methods), Fibroblasts (metabolism), Fibroblasts (transplantation), Humans, Lasers, Male, Methotrexate (administration & dosage), Methotrexate (pharmacokinetics), Mice, Mice, Inbred DBA, Mice, SCID, Microscopy, Confocal, Microscopy, Fluorescence, Optics and Photonics, Pentetic Acid (analogs & derivatives), Pentetic Acid (pharmacokinetics), Serum Albumin (administration & dosage), Serum Albumin (pharmacokinetics), Synovial Membrane (cytology), Synovial Membrane (metabolism), Synovial Membrane (transplantation).
- MESH :
- chemical , administration & dosage : Drug Carriers, Methotrexate, Serum Albumin.
- chemical , analogs & derivatives : Pentetic Acid.
- chemical , pharmacokinetics : Albumins, Drug Carriers, Methotrexate, Pentetic Acid, Serum Albumin.
- cytology : Synovial Membrane.
- drug therapy : Arthritis, Experimental, Arthritis, Rheumatoid.
- metabolism : Arthritis, Experimental, Arthritis, Rheumatoid, Fibroblasts, Synovial Membrane.
- methods : Drug Delivery Systems.
- pathology : Arthritis, Experimental, Arthritis, Rheumatoid.
- transplantation : Fibroblasts, Synovial Membrane.
- Animals, Cells, Cultured, Humans, Lasers, Male, Mice, Mice, Inbred DBA, Mice, SCID, Microscopy, Confocal, Microscopy, Fluorescence, Optics and Photonics.
Abstract
We reported recently that albumin is a suitable drug carrier for targeted delivery of methotrexate (MTX) to tumors. Due to pathophysiological conditions in neoplastic tissue, high amounts of albumin accumulate in tumors and are metabolized by malignant cells. MTX, covalently coupled to human serum albumin (MTX-HSA) for cancer treatment, is currently being evaluated in phase II clinical trials. Because synovium of patients with rheumatoid arthritis (RA) shares various features observed also in tumors, albumin-based drug targeting of inflamed joints might be an attractive therapeutic approach. Therefore, the pharmacokinetics of albumin and MTX in a mouse model of arthritis was examined. Additionally, uptake of albumin by synovial fibroblasts of RA patients and the efficacy of MTX and MTX-HSA in arthritic mice were studied. The results show that when compared with MTX, significantly higher amounts of albumin accumulate in inflamed paws, and significantly lower amounts of albumin are found in the liver and the kidneys. The protein is metabolized by human synovial fibroblasts in vitro and in vivo. MTX-HSA was significantly more effective in suppression of the onset of arthritis in mice than was MTX. In conclusion, albumin appears to be a suitable drug carrier in RA, most likely due to effects on synovial fibroblasts, which might increase therapeutic efficacy and reduce side effects of MTX.
PubMed: 12707361
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis.</title><author><name sortKey="Wunder, Andreas" uniqKey="Wunder A">Andreas Wunder</name><affiliation wicri:level="3"><nlm:affiliation>Department of Radiochemistry and Radiopharmacology, German Cancer Research Center, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiochemistry and Radiopharmacology, German Cancer Research Center, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="M Ller Ladner, Ulf" uniqKey="M Ller Ladner U">Ulf Müller-Ladner</name></author><author><name sortKey="Stelzer, Ernst H K" uniqKey="Stelzer E">Ernst H K Stelzer</name></author><author><name sortKey="Funk, J Rgen" uniqKey="Funk J">Jürgen Funk</name></author><author><name sortKey="Neumann, Elena" uniqKey="Neumann E">Elena Neumann</name></author><author><name sortKey="Stehle, Gerd" uniqKey="Stehle G">Gerd Stehle</name></author><author><name sortKey="Pap, Thomas" uniqKey="Pap T">Thomas Pap</name></author><author><name sortKey="Sinn, Hannsj Rg" uniqKey="Sinn H">Hannsjörg Sinn</name></author><author><name sortKey="Gay, Steffen" uniqKey="Gay S">Steffen Gay</name></author><author><name sortKey="Fiehn, Christoph" uniqKey="Fiehn C">Christoph Fiehn</name></author></titleStmt><publicationStmt><date when="2003">2003</date><idno type="RBID">pubmed:12707361</idno><idno type="pmid">12707361</idno><idno type="wicri:Area/Main/Corpus">003512</idno><idno type="wicri:Area/Main/Curation">003512</idno><idno type="wicri:Area/Main/Exploration">003390</idno></publicationStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Albumins (pharmacokinetics)</term><term>Animals</term><term>Arthritis, Experimental (drug therapy)</term><term>Arthritis, Experimental (metabolism)</term><term>Arthritis, Experimental (pathology)</term><term>Arthritis, Rheumatoid (drug therapy)</term><term>Arthritis, Rheumatoid (metabolism)</term><term>Arthritis, Rheumatoid (pathology)</term><term>Cells, Cultured</term><term>Drug Carriers (administration & dosage)</term><term>Drug Carriers (pharmacokinetics)</term><term>Drug Delivery Systems (methods)</term><term>Fibroblasts (metabolism)</term><term>Fibroblasts (transplantation)</term><term>Humans</term><term>Lasers</term><term>Male</term><term>Methotrexate (administration & dosage)</term><term>Methotrexate (pharmacokinetics)</term><term>Mice</term><term>Mice, Inbred DBA</term><term>Mice, SCID</term><term>Microscopy, Confocal</term><term>Microscopy, Fluorescence</term><term>Optics and Photonics</term><term>Pentetic Acid (analogs & derivatives)</term><term>Pentetic Acid (pharmacokinetics)</term><term>Serum Albumin (administration & dosage)</term><term>Serum Albumin (pharmacokinetics)</term><term>Synovial Membrane (cytology)</term><term>Synovial Membrane (metabolism)</term><term>Synovial Membrane (transplantation)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Drug Carriers</term><term>Methotrexate</term><term>Serum Albumin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Pentetic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Albumins</term><term>Drug Carriers</term><term>Methotrexate</term><term>Pentetic Acid</term><term>Serum Albumin</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Synovial Membrane</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Arthritis, Experimental</term><term>Arthritis, Rheumatoid</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Arthritis, Experimental</term><term>Arthritis, Rheumatoid</term><term>Fibroblasts</term><term>Synovial Membrane</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Drug Delivery Systems</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Arthritis, Experimental</term><term>Arthritis, Rheumatoid</term></keywords><keywords scheme="MESH" qualifier="transplantation" xml:lang="en"><term>Fibroblasts</term><term>Synovial Membrane</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Humans</term><term>Lasers</term><term>Male</term><term>Mice</term><term>Mice, Inbred DBA</term><term>Mice, SCID</term><term>Microscopy, Confocal</term><term>Microscopy, Fluorescence</term><term>Optics and Photonics</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We reported recently that albumin is a suitable drug carrier for targeted delivery of methotrexate (MTX) to tumors. Due to pathophysiological conditions in neoplastic tissue, high amounts of albumin accumulate in tumors and are metabolized by malignant cells. MTX, covalently coupled to human serum albumin (MTX-HSA) for cancer treatment, is currently being evaluated in phase II clinical trials. Because synovium of patients with rheumatoid arthritis (RA) shares various features observed also in tumors, albumin-based drug targeting of inflamed joints might be an attractive therapeutic approach. Therefore, the pharmacokinetics of albumin and MTX in a mouse model of arthritis was examined. Additionally, uptake of albumin by synovial fibroblasts of RA patients and the efficacy of MTX and MTX-HSA in arthritic mice were studied. The results show that when compared with MTX, significantly higher amounts of albumin accumulate in inflamed paws, and significantly lower amounts of albumin are found in the liver and the kidneys. The protein is metabolized by human synovial fibroblasts in vitro and in vivo. MTX-HSA was significantly more effective in suppression of the onset of arthritis in mice than was MTX. In conclusion, albumin appears to be a suitable drug carrier in RA, most likely due to effects on synovial fibroblasts, which might increase therapeutic efficacy and reduce side effects of MTX.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">12707361</PMID><DateCreated><Year>2003</Year><Month>04</Month><Day>22</Day></DateCreated><DateCompleted><Year>2003</Year><Month>08</Month><Day>13</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-1767</ISSN><JournalIssue CitedMedium="Print"><Volume>170</Volume><Issue>9</Issue><PubDate><Year>2003</Year><Month>May</Month><Day>1</Day></PubDate></JournalIssue><Title>Journal of immunology (Baltimore, Md. : 1950)</Title><ISOAbbreviation>J. Immunol.</ISOAbbreviation></Journal><ArticleTitle>Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis.</ArticleTitle><Pagination><MedlinePgn>4793-801</MedlinePgn></Pagination><Abstract><AbstractText>We reported recently that albumin is a suitable drug carrier for targeted delivery of methotrexate (MTX) to tumors. Due to pathophysiological conditions in neoplastic tissue, high amounts of albumin accumulate in tumors and are metabolized by malignant cells. MTX, covalently coupled to human serum albumin (MTX-HSA) for cancer treatment, is currently being evaluated in phase II clinical trials. Because synovium of patients with rheumatoid arthritis (RA) shares various features observed also in tumors, albumin-based drug targeting of inflamed joints might be an attractive therapeutic approach. Therefore, the pharmacokinetics of albumin and MTX in a mouse model of arthritis was examined. Additionally, uptake of albumin by synovial fibroblasts of RA patients and the efficacy of MTX and MTX-HSA in arthritic mice were studied. The results show that when compared with MTX, significantly higher amounts of albumin accumulate in inflamed paws, and significantly lower amounts of albumin are found in the liver and the kidneys. The protein is metabolized by human synovial fibroblasts in vitro and in vivo. MTX-HSA was significantly more effective in suppression of the onset of arthritis in mice than was MTX. In conclusion, albumin appears to be a suitable drug carrier in RA, most likely due to effects on synovial fibroblasts, which might increase therapeutic efficacy and reduce side effects of MTX.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wunder</LastName><ForeName>Andreas</ForeName><Initials>A</Initials><Affiliation>Department of Radiochemistry and Radiopharmacology, German Cancer Research Center, Heidelberg, Germany.</Affiliation></Author><Author ValidYN="Y"><LastName>Müller-Ladner</LastName><ForeName>Ulf</ForeName><Initials>U</Initials></Author><Author ValidYN="Y"><LastName>Stelzer</LastName><ForeName>Ernst H K</ForeName><Initials>EH</Initials></Author><Author ValidYN="Y"><LastName>Funk</LastName><ForeName>Jürgen</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Neumann</LastName><ForeName>Elena</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Stehle</LastName><ForeName>Gerd</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Pap</LastName><ForeName>Thomas</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Sinn</LastName><ForeName>Hannsjörg</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Gay</LastName><ForeName>Steffen</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Fiehn</LastName><ForeName>Christoph</ForeName><Initials>C</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType><PublicationType>Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Immunol</MedlineTA><NlmUniqueID>2985117R</NlmUniqueID><ISSNLinking>0022-1767</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Albumins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Drug Carriers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Serum Albumin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>indium DTPA-albumin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>methotrexate-serum albumin</NameOfSubstance></Chemical><Chemical><RegistryNumber>7A314HQM0I</RegistryNumber><NameOfSubstance>Pentetic Acid</NameOfSubstance></Chemical><Chemical><RegistryNumber>YL5FZ2Y5U1</RegistryNumber><NameOfSubstance>Methotrexate</NameOfSubstance></Chemical></ChemicalList><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Albumins</DescriptorName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Arthritis, Experimental</DescriptorName><QualifierName MajorTopicYN="N">drug therapy</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName><QualifierName MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName MajorTopicYN="Y">drug therapy</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName><QualifierName MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Drug Carriers</DescriptorName><QualifierName MajorTopicYN="N">administration & dosage</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Drug Delivery Systems</DescriptorName><QualifierName MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Fibroblasts</DescriptorName><QualifierName MajorTopicYN="N">metabolism</QualifierName><QualifierName MajorTopicYN="N">transplantation</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Lasers</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Methotrexate</DescriptorName><QualifierName MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice, Inbred DBA</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice, SCID</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Microscopy, Confocal</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Microscopy, Fluorescence</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Optics and Photonics</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Pentetic Acid</DescriptorName><QualifierName MajorTopicYN="Y">analogs & derivatives</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Serum Albumin</DescriptorName><QualifierName MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Synovial Membrane</DescriptorName><QualifierName MajorTopicYN="N">cytology</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName><QualifierName MajorTopicYN="N">transplantation</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2003</Year><Month>4</Month><Day>23</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2003</Year><Month>8</Month><Day>14</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2003</Year><Month>4</Month><Day>23</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">12707361</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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