[Nanosystems and targeted transport of medicinal preparations to the brain].

Intense efforts in the last decades have resulted in numerous inventions to improve drug delivery to CNS. Some of them have significant potential for clinical applications. At the same time, the variety of these strategies is in itself indicative of great difficulties inherent in the transfer of therapeutic and imaging agents across the blood-brain barrier. Combination of several approaches, such as encapsulation of drugs in nanocontainers, incorporation in micellar nanostructures, the use of Pluronic "unimers" for inhibition of drug efflux in endothelial cells of brain capillaries, appears to be the most promising modality. The same refers to the methods of intracellular transport of drug suspensions developed recently. All these achievements provide a solid basis for the further improvement of drug pharmacokinetic properties, reduction of systemic toxicity, increase of therapeutic efficacy, and earlier diagnosis of CNS pathology.

[Direct drug delivery to the brain].

The authors of the review discuss the present-day state of and promising approaches to directed delivery of biological agents into the brain. Special attention is drawn to micellar and liposomal transport through the blood-brain barrier (BBB) targeted by immunochemical vectors, such as native or hydrophobized antibodies to specific antigens located at the BBB or in the brain parenchyma.

[Production and characteristics of PEGylated immunoliposome transport vectors specific for neural tissue astrocytes].

PEGylated (stealth) immunoliposomes covalently linked to antibodies against human gliofibrillary acidic protein (GFAP) were prepared by coupling the thiolated monoclonal anti-GFAP antibodies, D4, with a maleimide derivative of the phosphatidyl ethanolamine of the liposomal membrane. Depending on the initial protein-to-lipid ratios, the immunoliposomes prepared (with a diameter of about 70 nm) were coupled with 60 to 240 molecules of the antibodies. In vitro experiments with cultures of the embryonic rat brain astrocytes demonstrated a specific binding of these immunoliposomes, which could be inhibited by the preincubation of the cells with free non-coupled D4 but not with non-specific antibodies. Administered intravenously into rats, the immunoliposomes exhibited a kinetic behaviour typical for the PEGylated liposomes: after 24 h, approximately 20% of the doses injected were still present in the blood; the elimination rate constants were 0.05-0.09 h(-1), the elimination half-lives were 8-15 h. With such a systemic longevity, as well as with such a specificity, these immunoliposomes, non-penetrating through intact blood-brain barrier (BBB), should be useful in delivering pharmacological agents to glial brain tumours (which continue to express GFAP) or to other pathological loci in the brain with a partially disintegrated BBB.

[Liposome-oriented transport of therapeutic drugs]. / Napravlennyi transport lekarstvennykh sredstv s pomoshch'iu liposom.

The attempts to use liposomes as containers for the transport of therapeutic drugs have been undertaken during the recent 40 years. However, the first success was achieved only in the 80-ies, when the sterically stabilized liposomes were invented. It was found that the liposome biological layer modified through, adding to it, certain polymers prolonged the blood circulation and reduced the capture of liposomes by RES cells. Elaboration of immunoliposomes, i.e. those conjugated with antibodies, was the next step in the path of perfecting the liposomes as a transport tool for the sake of binding with target-cells and to ensure the address-oriented delivery of drugs to a pathology focus. Preclinical and clinical testing of liposome-form of antitumor drugs witnessed to their lower toxicity and better pharmacokinetic indices; besides, they selectively accumulate themselves in tumor cells and have a more pronounced therapeutic effect even at lower doses of drugs in case of tumors resistant to the already made chemotherapy.

[Liposomal formulations of anthracycline antibiotics]. / Liposomal'nye formy antratsiklinovykh antibiotikov.

Anthracycline antibiotics with significant antitumor activity are widely used for treatment of various oncologic diseases in spite of their poor pharmacokinetics and severe side-effects. To improve the efficacy of treatment of oncologic patients, liposomal formulations of the anthracycline antibiotics, such as Doxil, TLC D-99, and DaunoXome, have been developed. Pharmacokinetic parameters of liposomal doxorubicin and daunorubicin differ markedly from the parameters of their free formulations. Liposomal anthracyclines display a prolonged circulation time, reduced clearance, smaller volume of distribution, and lower toxicity. Doxil and DaunoXome have been licensed for treatment of AIDS-related Kaposi's sarcoma. Entrapment of anthracycline antibiotics into liposomes coupled with monoclonal antibodies enhances their uptake by tumor cells.

[Prostate-specific membrane antigen and its role in diagnosis of prostate cancer]. / Prostaticheskii spetsificheskii membrannyi antigen i ego rol' v diagnostike raka predstatel'noi zhelezy.

This paper reviews recent achievements of the employment of prostate specific membrane antigen in the diagnostics of prostate cancer.

[Use of ion-exchange sorbents for determining drug preparations and their metabolites in biological fluids by high-performance liquid chromatography]. / Primenenie ionoobmennykh sorbentov pri opredelenii lekarstvennykh preparatov i ikh metabolitov v biologicheskikh zhidkostiakh metodom vysokoéffektivnoi zhidkostnoi khromatografii.

High performance liquid chromatography has acquired great importance recently for an analysis of the drugs in biological fluids of the body. Phase inversion sorbents are particularly widely used today. However, the use of ion-exchange sorbents is fairly promising for an analysis of the drugs capable of ionizing in an aqueous solution. The authors illustrate the use of the latter ones for determination in the blood, urine and saliva of man of a number of the cardiologic drugs (etmozine, nonachlazine, verapamil, prazosin, propranolol, nadolol). Ion-exchange sorbents make it possible to attain better results than inverse phase ones, since they retain the drugs selectively and do not retain the endogenous substances of lipid nature. As regards verapamil, prazosin and propranolol, the unchanged drug and polar metabolites could be determined jointly, with such a determination being not feasible with the use of phase inversion sorbents. Separation of the diastereoisomers of nadolol was achieved in the blood and urine of patients who received the drug.