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.

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.

In order to be useful, liposomal clodronate has to reach the infected organs. It cannot cross capillary walls. Until now, this method proved to be useful for depleting macrophages in liver, lymph nodes, lung, joints and other organs, including testis and peritoneal cavity. For achieving expected results, the drug has to be adequately administered.

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 temperature is very important. The suspension should never be frozen, and it should never be heated above 30 degrees of Celsius. The ideal temperature for keeping it is 4 degrees of Celsius. In any case, the suspension should be used within a few days. It is important to shake it well before dividing it into smaller dosages, because it tends to precipitate. It is important to get an even distribution, to achieve the proper concentration.

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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