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 bone diseases, but it become very interesting lately for depleting macrophages. Macrophages are destroying red blood cells, and they can be destroyed very effectively using this method. In fact, macrophages actually destroy themselves, and the results last for about one week. His gives a chance to other drugs.

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.

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.

Although it is possible to deplete macrophages in vitro, the method is specifically developed for in vivo research. Clodronate released from dead macrophages has very short half-life and will be rapidly removed by the kidneys. In the culture medium, dependent on the composition of the medium, it cannot escape so easily, and it can be partially accumulated by the surrounding cells.

The required temperature for storing and keeping this suspension is 4 degrees of Celsius. It is very important to take a good care about this temperature, and to use the product within a few days. Before using the product, it should reach a room temperature slowly. It means you have to leave it there for some time, and to shake it well before injecting it. Other things to remember are not to freeze the product ever, and not to expose it to temperatures above 30 degrees of Celsius.

The quantity may vary, but recommended intravenous injection should be less than 0,1 ml for every 10 grams of weight. This number can be higher in case of intraperitoneal injection of the drug. Clodronate is stored within the liposomes, and the concentration depends on its 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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