Clodronate Liposomes are a multilamellar liposome suspension in which clodronate is encapsulated in the aqueous compartments of the liposomes. PBS Liposomes are formulated and prepared identically to Clodronate Liposomes except that clodronate is not added to the liposomes. They have excellent activity, physical and chemical stability, and are convenient to use and handle. They are highly effective in removing macrophages from the body.

Mission: Target Technology  is committed to providing all individuals with the opportunity to get macrophages research experience. We offer technical expertise to advance comprehensive solutions to a broad range of macrophage research, with a particular focus on addressing the needs of macrophages isolation, enrichment, identification, depletion and trace.

Overview: Macrophages play an important role in immune and non-immune defence mechanisms. They form a first line of defence against bacterial, viral and other forms of microbiological contamination penetrating into the bodies of vertebrates. Macrophages are large cells, found in almost all bodily tissues where they can have varying forms and names (e.g. Kupffer cells, alveolar macrophages, microglia, osteoclasts, red pulp macrophages). Macrophages “scavenge”, they ingest and digest all foreign substances, microbes, cancer cells and cellular debris that might be potential pathogens. This process is called phagocytosis. Macrophages further regulate functions of many non-phagocytic cells, mainly through mediation of soluble molecules such as cytokines and chemokines. They are involved in innate immunity, adaptive immunity and can have (anti-) inflammatory effects.

Liposomes are artificially prepared spheres and consist of concentric phospholipid bilayers. When phospholipids are dispersed in water, the hydrophilic heads will make up both outer parts of the liposome, whereas the hydrophobic fatty acid groups will make up the inner part . Aqueous compartments separate the bilayers, and hydrophilic molecules can be dissolved in it, resulting in liposome-encapsulated molecules. 

Clodronate (dichloromethylene-bisphosphonate or Cl2MBP) is a hydrophilic molecule that can be encapsulated within phospholipid bilayers. Free clodronate does not easily cross cell membranes, and is rapidly cleared (i.e. within minutes) from circulation by the renal system. However, when entrapped in a liposome, the clodronate liposome is ingested by macrophages and cannot escape it . The phospholipid bilayers are digested by lysosomal phospholipases, whereas clodronate is not digested and remains in the macrophage. The more phospholipid bilayers and liposomes are ingested by the macrophage, the more clodronate will accumulate within the macrophage. Exceeding a certain intracellular concentration, clodronate will eliminate the macrophage by initiating its programmed cell death, i.e. apoptosis. Thus, clodronate liposomes can be used to study macrophage functioning by depletion of macrophages.

Clodronate liposomes are only able to deplete macrophages if they can be reached. Some tissues can form barriers for the liposomes. By choosing the right administration route of clodronate liposomes, particular organs or tissues can be depleted of macrophages.

PBS liposomes are mostly used for control experiments. However, these too can block phagocytosis by saturation for certain periods of time. PBS liposomes thus do not represent a control experiment with normal healthy, non-blocked, non-suppressed and non-activated macrophages. When comparing effects of clodronate liposomes with PBS liposomes, the effects can therefore be less than expected.