Byelorussian scientists have learned to synthesize new antituberculosis antibiotic drug formulation - liposomal rifampicin. Tests on laboratory animals have brought out clearly that the liposomal preparation is twice as efficacious as ordinary rifampicin. The point is that the researchers suggest that antibiotic should not be used by itself, but enclosed into lipidic containers - liposomes.

The idea of using liposomes as a vehicle for drug substance delivery into the patient's organism seems very appealing in general, and attempts to develop drug formulation of such kind have been made for years. On the one hand, the walls of these microscopical corpuscles (the diameter normally being less than 1 micron) are made of natural lipides - approximately the same as the ones making part of cellular membranes of human beings. Inside the liposomes, as well as between lipidic layers if liposomes are multilayer (like an onion, for example), there is either water or solution, in this case it is antibiotic solution. If antibiotic preparation (such as rifampicin) is hydrophobic, i.e. water-repellent, then it is embedded inside the layers between lipide molecules. At the same time, the preparation inside liposomes is less toxic for human beings and is better protected from destruction by blood enzymes.

If a patient respires the solution or, to be more precise, the suspension of such corpuscles, then the major part of liposomes together with the contents will get directly to the lungs, which is certainly very important for treatment of pulmonary forms of tuberculosis. The major part of antibiotic will make its way precisely to the target - into pulmonary macrophages, and this is very good. The reason is, firstly, because it is in the macrophages that mycobacteria of tuberculosis normally "settle down".
Secondly, macrophages are intended by nature to "devour" large alien objects and to destroy them. Alas, this does not work in case of tuberculosis pathogenes - they penetrate macrophages, but feel quite comfortable there.

But when such infected macrophage "eats up" a drug-containng liposome, the drug would kill the harmful mycobacteria. Therefore, in this case the liposome acts as a peculiar Trojan horse stuffed with antibiotic molecules.

The scientists failed so far to implement this remarkable idea for a rather trivial reason - they failed to produce satisfactory liposomes filled with rifampicin. Clinical picture requires a stable preparation to be well-preserved. That means that liposomes should be dried up - so that it only remained to add water to the ampoule and to stir it up before use. The liposomes suspension should be received, the liposomes being the same as before drying. Besides, the major part of antibiotic should be inside liposomes - otherwise, the entire undertaking loses meaning.

Specialists of the Minsk Institute of Biophysics and Cellular Engineering (National Academy of Sciences of Belorus) have managed to overcome these problems. The method they developed and patented allows to include the major part (up to 80 percent) of rifampicin in liposomes, and the liposomes themselves (previously frozen and dried up in vacuum) are stable enough.

Anyway, they can bear storage within 18 months and, according to the authors, can be well rehydrated. Simply speaking, in water they form homogeneous suspension without precipitate.

It should be noted that the researchers have managed to carry out a number of preclinical trials of the liposomes. They have found out that potential liposomic preparation is non-toxic and does not cause allergy. Experimental tuberculous infection model on mice has proved that it is 2.5 times more efficacious that an ordinary antibiotic solution. However, the scientists did not have time to complete preclinical trials -the project funding was suspended.

Olga Maximenko

Further information: S.V. Konev, Academician of the National Academy of Sciences of Belarus, Professor, Head of Laboratory of Biophysics and Cellular Engineering, Institute of Biophysics and Cellular Engineering, National Academy of Sciences of Belarus (Minsk), Tel.: (0172) 84-17-49, 84-22-52, Fax: (0172) 84-23-59, lbpm@biobel.bas-net.by