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.

Although clodronate itself wouldn't be able to successfully pass through all cell membranes, using liposomes as the vehicles efficiently solves this problem. Macrophages eagerly eat those liposomes, filling their cells with encapsulated clodronate, until the critical concentration is reached. At this point, they simply destroy themselves.

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.

Liposomes cannot get through capillary walls. This means that intravenous therapy can be useful for depleting macrophages in spleen, lung, joints, peritoneal cavity and other organs, including testis. Targeted therapy is also possible, using intraperitoneal injection. Macrophages won't be completely removed, but they are needed for different processes in the organism, anyway.

This method is developed for in vivo use. After destroying targeted macrophages, the drug gets released and enters the circulation. Thanks to the fact it has quite short half life once it reaches the circulation, it will be soon removed from the organism, and it won't be accumulated in surrounding cells. That's why this suspension cannot be so efficient in in vitro research.

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 method for making red blood cells eating macrophages destroy themselves proved to be very useful in different treatments. Quickly achieved results aren't permanent, they last for about one week. It is important to adequately administrate the drug, to use separate syringe for your test animals and to make sure to clean the skin before injecting the suspension. This way you will avoid different contamination. If you use the same syringe for all the animals, make sure to shake it each time.




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