Liposomes with a filling, or new potential in the fight with tuberculosis

A most promising version of the medicinal form to combat tuberculosis is under development by Belarusian scientists. First tests on animals have shown that it is really possible to essentially raise the effectiveness of therapy and reduce side effects. They are able to achieve this with the help of so-called liposomes, tiny lipid beads “filled” with a medicinal substance.

Belarusian scientists have learnt how to synthesize this new medicinal form of the anti-tuberculosis antibiotic – Liposome Rifampicin. Tests on laboratory animals have shown convincingly that the liposome preparation has double the effective action of regular Rifampicin. The fact is that the researchers propose the use of the antibiotic not on its own, but enclosed in lipid containers, in liposomes.

The idea to use liposomes as a means to deliver the medicine substance in the patient’s organism is, generally speaking, incredibly enticing and attempts to develop such a form of treatment have been ongoing for several years. The walls of these microscopic beads (their diameter is usually less than 1 micron) are made from natural lipids, roughly the same ones that are found in the composition of the human cell membrane. Inside the liposomes, and between the liposome layers if the liposomes are multi-layered, such as in an onion, either water or a solution is found, in this case the antibiotic. If the antibiotic preparation (such as Rifampicin, for example) is hydrophobic, meaning it does not like water, then it will settle inside the layers themselves, between the lipid molecules. Here, the preparation between the liposomes is less toxic to humans and is itself protected from being broken down by blood ferments.

If one breathes a suspension of such beads, the greater part of the liposomes, together with their content, will go directly to the lungs, which is of course of particular importance in the treatment of pulmonary forms of tuberculosis. Here a large part of the antibiotic is directed straight to the target, to the pulmonary macrophages, and this is very good. Firstly, it is in the macrophages that the tuberculosis bacteria tend to make their homes. And secondly the macrophages by their very nature are intended to devour major alien objects and destroy them. Alas, this does not work as far as the pathogens of tuberculosis are concerned; they penetrate the macrophages but feel quite at home there. However, when such an infected macrophage eats the liposome with the medicine, it kills off the harmful bacteria. One could say that the liposome in this sense acts distinctly like a Trojan horse, stuffed with molecules of the antibiotic.

To date it has not been possible to realize this wonderful idea, and for a really banal reason – It has not been possible to make satisfactory liposomes with Rifampicin. For clinical practice a stable, well-preserved preparation is required. This means that the liposomes have to be dried so that only water needs to be added to the ampoule and the ampoule shaken prior to use. Here a liposome suspension should result such as in the initial state, prior to drying. Furthermore, a large part of the antibiotic should be inside the liposome or else the entire plan has no point.

Staff at the Minsk-based Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus (NASB) has succeeded in overcoming these problems. The method they have developed and patented enables the inclusion of a large proportion (up to 80 percent) of Rifampicin into the liposomes, while the liposomes themselves, first frozen and dried in a vacuum, are suitably stable. In any case they can be stored for 18 months and, state the authors, they rehydrate well, meaning they form a uniform suspension in water without sediment.

It is worth stating that the scientists have also conducted a number of preclinical trials of their liposomes. They discovered that the potential liposome preparation is non-toxic and non-allergenic. Based on a model experimental tuberculosis infection in mice it was established that it is two-and-a-half times more effective than a regular solution of the antibiotic.

For additional information please contact:

Academician of NASB Professor Sergei Konev,
Head of Laboratory of Biophysics and Cell Engineering
of the Institute of Biophysics and Cell Engineering of NASB (Minsk)
Tel: (+375 172) 84-17-49, 84-22-52
Fax: (+375 172) 84-23-59
Email: lbpm@biobel.bas-net.by