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The drug formulations of antituberculous remedy rifampicin in nanoparticles less than 30 nm based on soy phosphatidylcholine and sodium oleate was elaborated in Institute of Biomedical Chemistry. The distribution of rifampicin in blood plasma fractions after incubation with this formulation and with free rifampicin was studied. This goal was stimulated by the literature data about activation of macrophages LDL receptors in cases of M. tuberculosis infection. Plasma was incubated 30 min with free rifampicin or rifampicin encapsulated into the nanoformulation followed by ultracentrifugation and subsequent rifampicin determination by HPLC in lipoprotein fractions. In the case of free rifampicin it appeared mainly in the plasma protein fraction and in HDL (41% and 38%, correspondentely). But after incubation of rifampicin in nanoparticles the drug redistribution was observed. Its proportion in these factions decreased 2-3-fold, and it was found mainly in LDL (60% as compared with 21% for free rifampicin). The increased association of rifampicin encapsulated into phospholipid nanoparticles with LDL is considered as facilitating factor for macrophages delivery and thus for antituberculosis efficiency as well.V Institute biomeditsinskoĭ khimii razrabotana i zapatentovana lekarstvennaia kompozitsiia protivotuberkuleznogo preparata rifampitsina, vstroennogo v nanochastitsy s diametrom 20-30 nm iz soevogo fosfatidilkholina s dobavleniem oleata natriia. Iskhodia iz dannykh literatury ob aktivatsii na poverkhnosti makrofagov retseptorov k lipoproteinam nizkoĭ plotnosti (LNP) pri infitsirovanii M. tuberculosis i vospalenii, v dannoĭ rabote issledovali raspredelenie rifampitsina po komponentam plazmy krovi in vitro pri inkubatsii kak co svobodnym rifampitsinom, tak i v sostave razrabotannoĭ nanokompozitsii. Posle inkubatsii v techenie 30 min plazmu krovi razdeliali ul'tratsentrifugirovaniem, i v poluchennykh fraktsiiakh lipoproteinov metodom VÉZhKh opredeliali soderzhanie rifampitsina. Polucheno, chto posle inkubatsii s plazmoĭ svobodnogo rifampitsina on obnaruzhivalsia v osnovnom v belkovoĭ fraktsii i v lipoproteinakh vysokoĭ plotnosti (LVP) (41% i 38%, sootvetstvenno), a pri inkubatsii rifampitsina v nanochastitsakh dolia lekarstva v étikh fraktsiiakh snizhalas' v 2-3 raza, i ono prisutstvovalo preimushchestvenno v LNP (60% po sravneniiu s 21% dlia svobodnogo rifampitsina). Povyshennaia assotsiatsiia rifampitsina s LNP rassmatrivaetsia kak faktor povysheniia ego dostavki v makrofagi, a sledovatel'no, i protivotuberkuleznoĭ aktivnosti.

Zebrafish (Danio rerio) are now firmly established as a powerful research model for many areas of biology and medicine. Here, we review some achievements of zebrafish - based assays for modeling human diseases and for drug discovery and development. For drug discovery, zebrafish are especially valuable in the earlier stages of research as they provide a model organism to demonstrate a new treatment's efficacy and toxicity before more costly mammalian models are used. This review provides examples of compounds known to be toxic to humans that have been demonstrated to functional similarly in zebrafish. Major advantages of zebrafish embryons are that they are readily permeable to small molecules added to their incubation medium and the transparent chorion enables the easy observation of development. Assay of acute toxicity (LC50 estimation) in embryos can also include the screening for developmental disorders as an indicator of teratogenic effects. We used zebrafish for toxicity testing of new drugs on the base of phospholipid nanoparticles. The organization of the genome and the pathways controlling signal transduction appear to be highly conserved between zebrafish and humans that allow using zebrafish for modeling of human diseases some examples of which are illustrated in this paper.