| Characterisation and tumour targeting of PEGylated polylysine dendrimers bearing doxorubicin via a pH labile linker. | |
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MedLine Citation:
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PMID: 21315119 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Polylysine dendrimers have potential as biodegradable vectors for the delivery of cytotoxic drugs to solid tumours. Here, the cytotoxicity, drug release and tumour targeting properties of Generation 5 PEGylated polylysine dendrimers comprising an outer generation of L-lysine or succinimyldipropyldiamine (SPN) and containing doxorubicin (DOX) linked through an acid labile 4-(hydrazinosulfonyl) benzoic acid (HSBA) linker have been characterised. Less than 10% of the DOX load was released from LYS or SPN dendrimers in pH 7.4 buffer over 3days. In contrast approximately 100% release was evident at pH 5. The DOX-conjugated dendrimers also retained similar cytotoxic properties to free DOX in in vitro cell culture studies (presumably as a result of in situ liberation of free DOX). The clearance patterns of the DOX conjugated SPN and all-lysine dendrimers were similar to the equivalent non-DOX conjugated systems, however the SPN dendrimers showed reduced metabolic lability and increased uptake into RES organs when compared to the equivalent all-lysine dendrimers. In vivo assessment of the DOX-conjugated, PEGylated polylysine dendrimers (both SPN and LYS constructs) in rats bearing Walker 256 tumours revealed higher uptake into tumour tissue when compared with control tissue such as muscle (~8 fold) and heart (~3 fold). The data suggest that polylysine dendrimers containing DOX conjugated via an acid labile HSBA linker may provide a mechanism to target the delivery of DOX to tumours. |
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Authors:
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Lisa M Kaminskas; Brian D Kelly; Victoria M McLeod; Gian Sberna; David J Owen; Ben J Boyd; Christopher J H Porter |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-8 |
Journal Detail:
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Title: Journal of controlled release : official journal of the Controlled Release Society Volume: - ISSN: 1873-4995 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8607908 Medline TA: J Control Release Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2010. Published by Elsevier B.V. |
Affiliation:
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Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville campus), 381 Royal Pde, Parkville, VIC, 3052, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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