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14 July 2013

Liposomal Clodronate Therapy For Depleting Macrophages

By Roxanne Cruz


Liposomal clodronate therapy is a very useful drug formulation for treating autoimmune hemolytic anemia. This particular autoimmune disease destroys red blood cells. Usual therapies include the use of corticosteroids and splenectomy, but this one gives very fast and promising results by destroying macrophages.

Clodronate was successfully used for treating different osteolytic bone diseases. In various researches, it proved itself to be very useful in so called liposome mediated macrophage suicide technique. This method of depleting macrophages provides very good results in a very short time. This is especially important when such fast results are needed for successful treatment.

The drug cannot pass phospholipid bi-layers of liposomes and cell membranes. On the other hand, macrophages are very interested in swallowing liposomes. If they are used as vehicles for transporting drug into organs, the drug will be released into the cell. When the concentration becomes large enough, the macrophage cell will destroy itself.

The suspension itself is non-toxic. The released drug, once it reaches the circulation, is safely removed from the body by the renal system. The results are very fast, and although they aren't permanent, they can be very useful in different treatments.

Of course, this method is successful only if liposomal clodronate reaches the macrophages to destroy. Given the fact that liposomes cannot cross capillary walls, they can destroy the macrophage in the liver, lung, spleen, lymph nodes, joints and peritoneal cavity. If liposomes are adequately administered, they can also destroy macrophages in testis.

This method was designed for destroying macrophages in vivo. Although it can be used in in vitro research as well, the problem is that it cannot be removed from the medium so effectively this way. It means it could be accumulated in different cells, and affect your final results. In living organism, it is successfully removed once in circulation, because the kidneys take very good care about it.

The suspension should be stored at 4 degrees Celsius, and it should never be frozen, or heated above 30 degrees Celsius. It should be gently shaken or stirred before injecting it, to get an even distribution of liposomes over the entire suspension, because liposomes tend to precipitate. It is especially important to leave the mixture on room temperature long enough to get the opportunity to reach it before injection.

Although the concentration you use can vary, it shouldn't extend 0,1 ml for 10 g of body weight, at least not for intravenous application. Targeted intraperitoneal application can involve larger concentration. In any case, the suspension concentration is depending on the drug solubility.

Liposomal clodronate therapy will effectively destroy macrophages. The absence of macrophages may cause an increase in e. G., virus titers, bacteria or yeasts. Test animals should always be perfectly clean where injected, to avoid possible microbial contamination. You should always shake the syringe, to get a homogeneous suspension, especially if you use the same one on all your test animals, which is not recommended.




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