Liposomal Clodronate Therapy For Depleting Macrophages

By Roxanne Cruz


Liposomal Clodronate is lately used in many medical researches, mainly as a treatment for autoimmune hemolytic anemia, also known as AIHA. Although some other methods proved to be useful as well, especially splenectomy and the use of corticosteroids, this method could be very useful for achieving good results in significantly shorter period of time.

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.

Clodronate itself cannot pass different cell membranes. When encapsulated within liposomes, they will surely be eagerly eaten by different macrophages. When the drug concentration reach the expected level within the macrophage cell, the result is the destruction of this cell. To be more precise, it is irreversibly damaged and dies by apoptosis.

This drug itself is not toxic, and when it is finally released from those dead macrophage cells, it has very short half-life in the circulation. This means that it will soon be completely removed from the organism by the renal system. Specificity of this method is that these ingredients give very quick results. This is especially important in cases where it is necessary to get a quick response to therapy.

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.

Intravenous injection should not be more than 0.1 ml per 10 grams of body weight. For intraperitoneal injection, this volume may be increased considerably. However, the concentration the drug in the aqueous compartments within the liposomes is limited by the solubility of clodronate.

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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