samedi 20 juillet 2013

Some Facts About Liposomal Clodronate

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 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.

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.

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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