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Liposomal Clodronate Therapy For Depleting Macrophages

By Roxanne Cruz


Liposomal clodronate therapy is used for depleting macrophages. It can be very useful for achieving very fast results in the treatment of different autoimmune diseases, including hemolytic anemia. In this case, macrophages destroy red blood cells, and this therapy makes them destroy themselves very effectively, in a short 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.

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.

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.

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 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.

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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