[Experimental basis for the use of new dosage forms of doxorubicin for correction of its hepatotoxic, prooxidant and immunosuppressory effects]. / Eksperimental'noe obosnovanie ispol'zovaniia novykh lekarstvennykh form doksorubitsina dlia korrektsii ego gepatotoksicheskogo, prooksidatnogo i immunosupressornogo deistviia.

The study was aimed at design of new dosage forms of doxorubicin (films, erythrocyte vehicles) for correction of its hepatotoxic, prooxidant and immunosuppressory effects. The experiments were performed on Wistar rats with the use of doxorubicin of Lens-Pharm (Moscow) and auxiliary substances meeting the requirements of the standards. Technology for preparation of doxorubicin-entrapped films was developed and the optimal polymer for the vehicle was recommended, i.e. oxypropylmethylcellulose Methocel 65 Hg 50 providing preservation of the antimicrobial activity. Conditions for storage of the antibiotic-entrapped films were determined. The main qualitative indices of the antibiotic-entrapped films were shown to be stable during the storage for 12 months. Erythrocyte-vehicles with entrapped doxorubicin were prepared. Antibiotic-free erythrocyte vehicles were found to preserve their ability to entrap doxorubicin for 9 days and the doxorubicin-entrapped erythrocyte vehicles were stable for 48 hours. A procedure for spectrophotometric qualitative evaluation of doxorubicin entrapping into the films and erythrocyte vehicles was developed. It was observed that administration of doxorubicin immobilized in the films had a stabilizing effect on the immunity status, the level of lipid peroxidation, the potency of the antioxidant system, cytolysis and cholestasis. Administration of the doxorubicin entrapped in the erythrocyte vehicles stimulated the body immune response, normalized the indices of the lipid peroxidation--antioxidant system and the state of the hepatic cells in the laboratory animals infected by staphylococci.

[Immunomodulating, antioxidant and hepatoprotective effects of immobilized dosage forms of rifampicin and cephalexin]. / Immunomoduliruiushchee, antioksidantnoe i gepatoprotektornoe deistvie immobilizovannykh form rifampitsina i tsefaleksina.

The aim of the study was to lower the immunosuppressory, prooxidant and hepatotoxic effects of rifampicin and cephalexin by their immobilization in erythrocyte vehicles. The experiments were performed on Wistar rats with the use of rifampicin, cephalexin and lysozyme (ZAO Ferane) and hemodes (6% aqueous saline solution of low molecular polyvinylpyrrolidone, mol. wt. 12600+/-2700). Rifampicin- and cephalexin-entrapped erythrocytes were prepared. Spectrophotometric procedures for quantitative assay of the immobilized antibiotics were developed. The impact of the solution concentration and incubation time on the level of the antibiotic entrapping was studied. The erythrocyte vehicles were shown to be able to entrap the antibiotics for 9 days and to preserve their stability for 24 hours. It was observed that the increase of the immunosuppressory, prooxidant and hepatotoxic effects of the antibiotics administered without the vehicles to the laboratory animals infected by staphylococci was dose-dependent. The use of the antibiotics entrapped in the erythrocyte vehicles stimulated the immune reactivity of the animals and normalized the indices of lipid peroxidation, the antioxidant system, cytolysis and cholestasis.

[Immunomodulating action of antibiotics in health and in staphylococcal infection]. / Immunomoduliruiushchee deistvie antibiotikov v norme i pri infitsirovanii stafilokokkom.

Benzylpenicillin, streptomycin and gentamicin injected to the mice with Staphylococcus infection increased the immunosuppression induced by the staphylococci. The highest immunosuppressing action was induced by benzylpenicillin. Red blood cells of healthy and especially infected animals showed in case of the allogenic transfer marked immunosuppressing properties. Injection of syngenic red blood cells extracorporeally treated with the antibiotics stimulated the immune response to SRBC in the mice but did not influence the response induced by LPS of Salmonella typhi. The red blood cells incubated in the presence of gentamicin (5000 micrograms) for 1 hour had the most pronounced immunostimulating properties. Benzylpenicillin and streptomycin extracorporal treatment of the red blood cells of the animals infected with staphylococci did not induce immunomodulating properties in them whereas the incubation in the presence of gentamicin resulted in the development of slightly pronounced immunostimulating properties.

[Correction of the immunomodulating action of antibiotics in health and in staphylococcal infection]. / Korrektsiia immunomoduliruiushchego deistviia antibiotikov v norme i pri stafilokokkovoi infektsii.

Administration of tocopherol acetate and essentiale to healthy animals not treated with antibiotics had no effect on the immune response induced by SRBC or LPS of Salmonella typhi. Administration of tocopherol acetate to the mice treated with streptomycin or gentamicin increased the response only to SRBC. Essentialle stimulated the development of the T-dependent and T-independent immune response in the animals treated with benzylpenicillin, streptomycin or gentamicin. Benzylpenicillin and streptomycin increased the suppressing effect of the Staphylococcus infection. Gentamicin had no effect on the immune response to SRBC and LPS. Tocopherol acetate and lysozyme increased the immune response to SRBC. Terrilitin did not influence the immune response to SRBC and LPS. Essentiale stimulated the response to both the T-dependent and T-independent antigens.