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 11.10.2007   Карта сайта     Language По-русски По-английски
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11.10.2007



Lanthanides get to the bones of the matter



10 October 2007



Lipophilic wrapping paper is helping lanthanides cross into cells. Kishor Wasan, Chris Orvig and colleagues at the University of British Columbia in Vancouver, Canada, say that their ion delivery method could lead to osteoporosis treatments.



"Lanthanides can replace calcium in bone and encourage bone formation by activating the cells responsible for bone production"

Lanthanides are already used in medicine as, for example, anticancer drugs and radiotherapy diagnostics. A limitation of lanthanide ions as orally-administered drugs, however, is their poor ability to cross cell membranes, particularly the intestine. 


To improve lanthanide bioavailability, Orvig and his team masked lanthanide ions in complexes with lipophilic hydroxypyridinones and hydroxypyrones. The researchers used a human colon carcinoma cell line to test whether the complexes could cross cell membranes. They found that the most lipophilic of the hydroxypyridinone complexes increased lanthanide uptake into cells.


Healthy bone tissue and diseased tissue from osteoporosis


The team also added the complexes to hydroxyapatite, a calcium phosphate mineral similar to that found in bone. Lanthanides bind strongly to the mineral through their high affinity for phosphate. The team found that the complexes deliver lanthanides to the hydroxyapatite where they bind without disturbing its structure. 


Inadequate calcium uptake causes bone disease by reducing bone mineral density, said Orvig. Lanthanides can replace calcium in bone and encourage bone formation by activating osteoblasts - the cells responsible for bone production. At the same time, lanthanides repress the cells involved in bone breakdown or resorption. It is this ability to mimic calcium ion function that makes lanthanides potential therapeutics for bone density disorders. 


Orvig cautioned that there are still major hurdles to be overcome, 'including the pharmaceutical industry's perception that metal-containing drugs are toxic.' This research showed that lanthanide-ligand complexes are less toxic than the platinum-based drug cisplatin and in future research Orvig aims to develop non-toxic compounds that can be taken orally.  


Peter Sadler, an expert in metallodrug design at the University of Warwick, UK, described the exploration of the periodic table for medical use as an exciting field of research. 'Orvig has shown that pyridinone derivatives can control the cellular uptake of lanthanide ions, their toxicity and binding to hydroxyapatite. What will be interesting now is to find out whether these compounds are potential inhibitors of bone resorption for the treatment of osteoporosis.'


Janet Crombie




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