Thursday, July 25, 2013

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.

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.

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 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.

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.

Liposomal clodronate therapy will effectively destroy macrophages. The absence of macrophages may cause an increase in e. G., virus titers, bacteria or yeasts. Test animals should always be perfectly clean where injected, to avoid possible microbial contamination. You should always shake the syringe, to get a homogeneous suspension, especially if you use the same one on all your test animals, which is not recommended.




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