Pharmacokinetics, biodistribution, and anti-angiogenesis efficacy of diamino propane tetraiodothyroacetic acid-conjugated biodegradable polymeric nanoparticle

dc.contributor.authorLi, Weikun
dc.contributor.authorBharali, Dhruba J.
dc.contributor.authorLin, Qishan
dc.contributor.authorGodugu, Kavitha
dc.contributor.authorFujioka, Kazutoshi
dc.contributor.authorKeating, Kelly A.
dc.contributor.authorMousa, Shaker A.
dc.contributor.buuauthorYalçın, Murat
dc.contributor.departmentBursa Uludağ Üniversitesi/Veteriner Fakültesi/Fizyoloji Anabilim Dalı.tr_TR
dc.contributor.orcid0000-0002-5600-8162tr_TR
dc.contributor.researcheridAAG-6956-2021tr_TR
dc.contributor.scopusid57192959734tr_TR
dc.date.accessioned2023-03-23T13:13:51Z
dc.date.available2023-03-23T13:13:51Z
dc.date.issued2019-06-21
dc.description.abstractThe anti-angiogenic agent, diamino propane tetraiodothyroacetic acid (DAT), is a thyro-integrin (integrin alpha v beta 3) antagonist anticancer agent that works via genetic and nongenetic actions. Tetraiodothyroacetic acid (tetrac) and DAT as thyroid hormone derivatives influence gene expression after they transport across cellular membranes. To restrict the action of DAT to the integrin alpha v beta 3 receptors on the cell surface, we used DAT-conjugated PLGA nanoparticles (NDAT) in an active targeting mode to bind to these receptors. Preparation and characterization of NDAT is described, and both in vitro and in vivo experiments were done to compare DAT to NDAT. Intracellular uptake and distribution of DAT and NDAT in U87 glioblastoma cells were evaluated using confocal microscopy and showed that DAT reached the nucleus, but NDAT was restricted from the nucleus. Pharmacokinetic studies using LC-MS/MS analysis in male C57BL/6 mice showed that administration of NDAT improved the area under the drug concentration curve AUC(()(0-)(48 h)) by 4-fold at a dose of 3 mg/kg when compared with DAT, and C-max of NDAT (4363 ng/mL) was 8-fold greater than that of DAT (548 ng/ mL). Biodistribution studies in the mice showed that the concentrations of NDAT were higher than DAT/Cremophor EL micelles in heart, lung, liver, spleen, and kidney. In another mouse model using female NCr nude homozygous mice with U87 xenografts, tumor growth was significantly decreased at doses of 1 and 3 mg/kg of NDAT. In the chick chorioallantoic membrane (CAM) assay used to measure angiogenesis, DAT (500 ng/CAM) resulted in 48% inhibition of angiogenesis levels. In comparison, NDAT at low dose (50 ng/CAM) showed 45% inhibition of angiogenesis levels. Our investigation of NDAT bridges the study of polymeric nanoparticles and anti-angiogenic agents and offers new insight for the rational design of anti-angiogenic agents.en_US
dc.description.sponsorshipPharmaceutical Research Institute (PRI)en_US
dc.description.sponsorshipNanoPharmaceuticals LLC (Rensselaer, NY, USA)en_US
dc.identifier.citationLi, W. vd. (2019). 'Pharmacokinetics, biodistribution, and anti-angiogenesis efficacy of diamino propane tetraiodothyroacetic acid-conjugated biodegradable polymeric nanoparticle''. Scientific Reports, 9.en_US
dc.identifier.issn2045-2322
dc.identifier.pubmed31227723tr_TR
dc.identifier.scopus2-s2.0-85067797360tr_TR
dc.identifier.urihttps://doi.org/10.1038/s41598-019-44979-6
dc.identifier.urihttps://www.nature.com/articles/s41598-019-44979-6
dc.identifier.urihttp://hdl.handle.net/11452/31721
dc.identifier.volume9tr_TR
dc.identifier.wos000472477300005tr_TR
dc.indexed.pubmedPubMeden_US
dc.indexed.scopusScopusen_US
dc.indexed.wosSCIEen_US
dc.language.isoenen_US
dc.publisherNatureen_US
dc.relation.collaborationYurt dışıtr_TR
dc.relation.collaborationSanayitr_TR
dc.relation.journalScientific Reportsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectScience & technology - other topicsen_US
dc.subjectDependent cellular uptakeen_US
dc.subjectTargeted deliveryen_US
dc.subjectThyroid-hormoneen_US
dc.subjectClinical translationen_US
dc.subjectCancer-therapyen_US
dc.subjectCremophor elen_US
dc.subjectIn-vitroen_US
dc.subjectDrungen_US
dc.subjectPaclitaxelen_US
dc.subjectTetracen_US
dc.subject.emtreeBiomaterialen_US
dc.subject.emtreeNanoparticleen_US
dc.subject.emtreePolymeren_US
dc.subject.emtreePropaneen_US
dc.subject.emtreeTetraiodothyroacetic aciden_US
dc.subject.emtreeThyroxineen_US
dc.subject.emtreeAnimalen_US
dc.subject.emtreeC57BL mouseen_US
dc.subject.emtreeChemistryen_US
dc.subject.emtreeChickenen_US
dc.subject.emtreeChorioallantoisen_US
dc.subject.emtreeDrug effecten_US
dc.subject.emtreeDrug screeningen_US
dc.subject.emtreeFemaleen_US
dc.subject.emtreeGlioblastomaen_US
dc.subject.emtreeHumanen_US
dc.subject.emtreeMaleen_US
dc.subject.emtreeMetabolismen_US
dc.subject.emtreeNeovascularization (pathology)en_US
dc.subject.emtreeNude mouseen_US
dc.subject.emtreeProceduresen_US
dc.subject.emtreeTissue distributionen_US
dc.subject.emtreeTumor cell lineen_US
dc.subject.emtreeVascularizationen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBiocompatible materialsen_US
dc.subject.meshCell Line, tumoren_US
dc.subject.meshChickensen_US
dc.subject.meshChorioallantoic membraneen_US
dc.subject.meshFemaleen_US
dc.subject.meshGlioblastomaen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMice, inbred C57BLen_US
dc.subject.meshMice, nudeen_US
dc.subject.meshNanoparticlesen_US
dc.subject.meshNeovascularization, pathologicen_US
dc.subject.meshPolymersen_US
dc.subject.meshPropaneen_US
dc.subject.meshThyroxineen_US
dc.subject.meshTissue distributionen_US
dc.subject.meshXenograft model antitumor assaysen_US
dc.subject.scopusIntegrin; Thyroid Hormones; Nano-Diamino-Tetracen_US
dc.subject.wosMultidisciplinary sciencesen_US
dc.titlePharmacokinetics, biodistribution, and anti-angiogenesis efficacy of diamino propane tetraiodothyroacetic acid-conjugated biodegradable polymeric nanoparticleen_US
dc.typeArticle
dc.wos.quartileQ1en_US

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