Liposomal Clodronate For Treating Autoimmune Hemolytic Anemia

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 is a member of the family of bisphosphonates. It was first used as a treatment for osteolytic bone diseases. Thanks to its characteristics, now it is effectively used in liposome mediated macrophage suicide technique, for depleting macrophages from different organs and tissues. This targeted therapy is very successful in all previous medical research.

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.

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.

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 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.

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.

In liposomal clodronate therapy, the macrophage cell is irreversibly damaged and dies by apoptosis. It is recommended to use separate syringes for different animals. Make sure to shake the product well before dividing it in smaller doses. Make sure to clean well the areas where you plan to inject the suspension, to avoid different virus or bacteria contamination.




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