Liposomal Clodronate Therapy For Depleting Macrophages

By Roxanne Cruz


Liposomal clodronate therapy is a very useful drug formulation for treating autoimmune hemolytic anemia. This particular autoimmune disease destroys red blood cells. Usual therapies include the use of corticosteroids and splenectomy, but this one gives very fast and promising results by destroying macrophages.

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.

Although clodronate itself wouldn't be able to successfully pass through all cell membranes, using liposomes as the vehicles efficiently solves this problem. Macrophages eagerly eat those liposomes, filling their cells with encapsulated clodronate, until the critical concentration is reached. At this point, they simply destroy themselves.

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.

Liposomes cannot get through capillary walls. This means that intravenous therapy can be useful for depleting macrophages in spleen, lung, joints, peritoneal cavity and other organs, including testis. Targeted therapy is also possible, using intraperitoneal injection. Macrophages won't be completely removed, but they are needed for different processes in the organism, anyway.

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.

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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