Linked Life Data

19463870

Source:http://linkedlifedata.com/resource/pubmed/id/19463870

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-8-3
pubmed:abstractText
In search of optimizing siRNA delivery systems for systemic application, one critical parameter remains their stability in blood circulation. In this study, we have traced pharmacokinetics and biodistribution of each component of siRNA polyplexes formed with polyethylenimine 25 kDa (PEI) or PEGylated PEIs by in vivo real-time gamma camera recording, SPECT imaging, and scintillation counting of blood samples and dissected organs. In vivo behavior of siRNA and polymers were compared and interpreted in the context of in vivo stability of the polyplexes which had been measured by fluorescence fluctuation spectroscopy (FFS). Both pharmacokinetics and biodistribution of polymer-complexed siRNA were dominated by the polymer. PEGylated polymers and their siRNA polyplexes showed significantly less uptake into liver (13.6-19.7% ID of PEGylated polymer and 9.5-10.2% ID of siRNA) and spleen compared to PEI 25 kDa (liver deposition: 36.2% ID of polymer and 14.6% ID of siRNA). With non-invasive imaging methods we were able to predict both kinetics and deposition in living animals allowing the investigation of organ distribution in real time and at different time points. FFS measurements proved stability of the applied polyplexes under in vivo conditions which explained the different behavior of complexed from free siRNA. Despite their stability in circulation, we observed that polyplexes dissociated upon liver passage. Therefore, siRNA/(PEG-)PEI delivery systems are not suitable for systemic administration, but instead may be useful when the first-pass effect is circumvented, which is the case in local application.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1873-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
138
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
148-59
pubmed:meshHeading
pubmed-meshheading:19463870-Animals, pubmed-meshheading:19463870-Drug Carriers, pubmed-meshheading:19463870-Drug Compounding, pubmed-meshheading:19463870-Drug Stability, pubmed-meshheading:19463870-Gamma Cameras, pubmed-meshheading:19463870-HeLa Cells, pubmed-meshheading:19463870-Humans, pubmed-meshheading:19463870-Luciferases, pubmed-meshheading:19463870-Mice, pubmed-meshheading:19463870-Mice, Inbred BALB C, pubmed-meshheading:19463870-Polyethylene Glycols, pubmed-meshheading:19463870-Polyethyleneimine, pubmed-meshheading:19463870-RNA, Small Interfering, pubmed-meshheading:19463870-Spectrometry, Fluorescence, pubmed-meshheading:19463870-Tissue Distribution, pubmed-meshheading:19463870-Tomography, Emission-Computed, Single-Photon, pubmed-meshheading:19463870-Transfection, pubmed-meshheading:19463870-Ultrafiltration
pubmed:year
2009
pubmed:articleTitle
Stability of siRNA polyplexes from poly(ethylenimine) and poly(ethylenimine)-g-poly(ethylene glycol) under in vivo conditions: effects on pharmacokinetics and biodistribution measured by Fluorescence Fluctuation Spectroscopy and Single Photon Emission Computed Tomography (SPECT) imaging.
pubmed:affiliation
Department of Pharmaceutics and Biopharmacy, Philipps-Universität Marburg, Ketzerbach 63, 35037 Marburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't