Document Detail


Biodistribution of polymer hydrogel capsules for the delivery of therapeutics.
MedLine Citation:
PMID:  22659177     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A key phase in the development of intelligently designed nanoparticle delivery vehicles for new therapeutic agents is to gain an understanding of their interaction with tissues and cells. We report a series of in vitro and in vivo experiments aimed at tracking a potential delivery vehicle for therapeutic agents including vaccine peptides and drugs derived from poly (methacrylic acid) hydrogel capsules in certain organs and cell types. For the in vitro studies, two immortal liver-derived cell lines (Huh7 and Hepa1-6) and primary cultures of mouse hepatocytes were incubated with Alexa 647 labelled fluorescent capsules to track their internalisation and intracellular distribution by confocal microscopy. Capsules, 500nm in diameter were taken up into the cells in a time-dependent manner in all three cell lines. Capsules were observed in plasma membrane-derived vesicles within the cells. After 24 hours a significant proportion of the capsules were observed in lysosomes. To understand the behaviour of the capsules in vivo, Alexa 488 labelled fluorescent capsules were intravenously injected into Sprague-Dawley rats and after 24 hours the fate of the capsules in a number of organs was determined by flow cytometry and confocal microscopy. By flow cytometry, the majority of the capsules were detected in the spleen whilst similar numbers were found in the lung and liver. By confocal microscopy, the majority of the capsules were found in the liver and spleen with significantly less capsules in the lung, heart and kidney. Colocalisation of capsules with cell-type specific markers indicated that in lung, heart and kidney, the majority of the capsules were located in endothelial cells. In the spleen approximately 50% of the capsules were found in CD163-positive cells, whereas in the liver, almost all capsules were located in CD163-positive cells, indicating uptake by Kupffer cells. Electron microscopy confirmed the presence of capsules within Kupffer cells.
Authors:
Tracey Hinton; Paul Monaghan; Diane Green; Sander A A Kooijmans; Shuning Shi; Kerry Breheney; Mark Tizard; Joseph A Nicolazzo; Alexander N Zelikin; Kim Wark
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-29
Journal Detail:
Title:  Acta biomaterialia     Volume:  -     ISSN:  1878-7568     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-6-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101233144     Medline TA:  Acta Biomater     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
CSIRO Livestock Industries, Australian Animal Health Laboratory, 5 Portarlington Road, East Geelong Victoria 3219, Australia.
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