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 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.

Besides giving very fast and reliable results, this method has other qualities. The drug is completely non-toxic. It is developed for in vivo use, and once released from the destroyed macrophage cell, it will soon be removed by the kidneys. The drug has extremely short half life once in circulation. Quickly achieved results can be very useful, especially in combination with other therapies.

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 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.

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.

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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