Liposomal Clodronate Therapy For Depleting Macrophages

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.

This drug itself is not toxic, and when it is finally released from those dead macrophage cells, it has very short half-life in the circulation. This means that it will soon be completely removed from the organism by the renal system. Specificity of this method is that these ingredients give very quick results. This is especially important in cases where it is necessary to get a quick response to therapy.

Of course, this method is successful only if liposomal clodronate reaches the macrophages to destroy. Given the fact that liposomes cannot cross capillary walls, they can destroy the macrophage in the liver, lung, spleen, lymph nodes, joints and peritoneal cavity. If liposomes are adequately administered, they can also destroy macrophages in testis.

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 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.

The quantity may vary, but recommended intravenous injection should be less than 0,1 ml for every 10 grams of weight. This number can be higher in case of intraperitoneal injection of the drug. Clodronate is stored within the liposomes, and the concentration depends on its solubility.

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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