The effect of molecular weight on the biodistribution of hyaluronic acid radiolabeled with 111In after intravenous administration to rats.
Identifieur interne : 007C97 ( Main/Exploration ); précédent : 007C96; suivant : 007C98The effect of molecular weight on the biodistribution of hyaluronic acid radiolabeled with 111In after intravenous administration to rats.
Auteurs : RBID : pubmed:19007040English descriptors
- KwdEn :
- Animals, Biological Availability, Chromatography, High Pressure Liquid, Drug Compounding, Drug Stability, Hyaluronic Acid (administration & dosage), Hyaluronic Acid (chemistry), Hyaluronic Acid (pharmacokinetics), Indium Radioisotopes, Injections, Intravenous, Male, Metabolic Clearance Rate, Molecular Weight, Pentetic Acid (chemistry), Rats, Rats, Wistar, Tissue Distribution.
- MESH :
- chemical , administration & dosage : Hyaluronic Acid.
- chemical , chemistry : Hyaluronic Acid, Pentetic Acid.
- chemical , pharmacokinetics : Hyaluronic Acid.
- Animals, Biological Availability, Chromatography, High Pressure Liquid, Drug Compounding, Drug Stability, Indium Radioisotopes, Injections, Intravenous, Male, Metabolic Clearance Rate, Molecular Weight, Rats, Rats, Wistar, Tissue Distribution.
Abstract
Hyaluronic acid (HA), is a high molecular weight (HMW) glucosaminoglycan with significant acitivity, and which influences a number of physiological and pathological processes such as tumorogenesis, arthritis, etc. The aim of this study was to determine the difference in the biodistributional pathways of 111In-labeled diethylenetriaminepentaacetic acid-hyaluronic acid (111In-DTPA-HA) molecule of three different MWs (10, 100 and 450 kDA) in a rat model, and to determine possible relationships between the biodistribution and the MW of the investigated agent for future medical applications. 111In-DTPA-HA was prepared by mixing activated DTPA and activated HA, then adding 111InCl3 to the previously prepared mixture at pH 5,5 in an acetic buffer. Biodistributional studies were performed using 36 male Wistar rats aged 2 months and weighing 280 - 350 g. The radioactivity in the samples was measured via a radiometer and the radioactivity in the different organs, blood, plasma and urine was determined. It was found that 50-54% for 10 and 100 kDa and 80% for 450 kDa of the administered dose of radiolabel was present in the liver after 5 min. Other organs show no significant increase during the experimental period. The elimination of the radiolabel was mostly renal and in low molecular weight (LMW) form. Radioactivity remained in liver throughout the 72h experimental period. A difference in the biodistribution of 450 kDa and LMW radiolabeled molecules was found. Higher amounts of radiolabel were taken up by the liver when the 450 kDa molecule was used. LMW fractions were found in the urine, and could have been a product of non-enzymatic cleavage. The extended retention of radiolabel in the liver could be related to changes in the polarity of DTPA-HA molecules.
PubMed: 19007040
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Biodistributional studies were performed using 36 male Wistar rats aged 2 months and weighing 280 - 350 g. The radioactivity in the samples was measured via a radiometer and the radioactivity in the different organs, blood, plasma and urine was determined. It was found that 50-54% for 10 and 100 kDa and 80% for 450 kDa of the administered dose of radiolabel was present in the liver after 5 min. Other organs show no significant increase during the experimental period. The elimination of the radiolabel was mostly renal and in low molecular weight (LMW) form. Radioactivity remained in liver throughout the 72h experimental period. A difference in the biodistribution of 450 kDa and LMW radiolabeled molecules was found. Higher amounts of radiolabel were taken up by the liver when the 450 kDa molecule was used. LMW fractions were found in the urine, and could have been a product of non-enzymatic cleavage. The extended retention of radiolabel in the liver could be related to changes in the polarity of DTPA-HA molecules.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">19007040</PMID><DateCreated><Year>2008</Year><Month>11</Month><Day>14</Day></DateCreated><DateCompleted><Year>2008</Year><Month>12</Month><Day>16</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0378-7966</ISSN><JournalIssue CitedMedium="Print"><Volume>33</Volume><Issue>3</Issue><PubDate><MedlineDate>2008 Jul-Sep</MedlineDate></PubDate></JournalIssue><Title>European journal of drug metabolism and pharmacokinetics</Title><ISOAbbreviation>Eur J Drug Metab Pharmacokinet</ISOAbbreviation></Journal><ArticleTitle>The effect of molecular weight on the biodistribution of hyaluronic acid radiolabeled with 111In after intravenous administration to rats.</ArticleTitle><Pagination><MedlinePgn>149-57</MedlinePgn></Pagination><Abstract><AbstractText>Hyaluronic acid (HA), is a high molecular weight (HMW) glucosaminoglycan with significant acitivity, and which influences a number of physiological and pathological processes such as tumorogenesis, arthritis, etc. The aim of this study was to determine the difference in the biodistributional pathways of 111In-labeled diethylenetriaminepentaacetic acid-hyaluronic acid (111In-DTPA-HA) molecule of three different MWs (10, 100 and 450 kDA) in a rat model, and to determine possible relationships between the biodistribution and the MW of the investigated agent for future medical applications. 111In-DTPA-HA was prepared by mixing activated DTPA and activated HA, then adding 111InCl3 to the previously prepared mixture at pH 5,5 in an acetic buffer. Biodistributional studies were performed using 36 male Wistar rats aged 2 months and weighing 280 - 350 g. The radioactivity in the samples was measured via a radiometer and the radioactivity in the different organs, blood, plasma and urine was determined. It was found that 50-54% for 10 and 100 kDa and 80% for 450 kDa of the administered dose of radiolabel was present in the liver after 5 min. Other organs show no significant increase during the experimental period. The elimination of the radiolabel was mostly renal and in low molecular weight (LMW) form. Radioactivity remained in liver throughout the 72h experimental period. A difference in the biodistribution of 450 kDa and LMW radiolabeled molecules was found. Higher amounts of radiolabel were taken up by the liver when the 450 kDa molecule was used. LMW fractions were found in the urine, and could have been a product of non-enzymatic cleavage. The extended retention of radiolabel in the liver could be related to changes in the polarity of DTPA-HA molecules.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Svanovsky</LastName><ForeName>E</ForeName><Initials>E</Initials><Affiliation>Faculty of Pharmacy, Charles University, Heyrovskeho 1203, Hradec Králové, Czech Republic.</Affiliation></Author><Author ValidYN="Y"><LastName>Velebny</LastName><ForeName>V</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Laznickova</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Laznicek</LastName><ForeName>M</ForeName><Initials>M</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType><PublicationType>Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Eur J Drug Metab Pharmacokinet</MedlineTA><NlmUniqueID>7608491</NlmUniqueID><ISSNLinking>0378-7966</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Indium Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>7A314HQM0I</RegistryNumber><NameOfSubstance>Pentetic Acid</NameOfSubstance></Chemical><Chemical><RegistryNumber>9004-61-9</RegistryNumber><NameOfSubstance>Hyaluronic Acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Biological Availability</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Chromatography, High Pressure Liquid</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Drug Compounding</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Drug Stability</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Hyaluronic Acid</DescriptorName><QualifierName MajorTopicYN="N">administration & dosage</QualifierName><QualifierName MajorTopicYN="N">chemistry</QualifierName><QualifierName MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Indium Radioisotopes</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Injections, Intravenous</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Metabolic Clearance Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Molecular Weight</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Pentetic Acid</DescriptorName><QualifierName MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Rats, Wistar</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Tissue Distribution</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2008</Year><Month>11</Month><Day>15</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2008</Year><Month>12</Month><Day>17</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2008</Year><Month>11</Month><Day>15</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">19007040</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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