[Experimental basis for the use of new dosage forms of doxorubicin for correction of its hepatotoxic, prooxidant and immunosuppressory effects].
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.
Prokopenko
L G
LG
Lazarev
A I
AI
Siplivyĭ
G V
GV
Kukureka
A V
AV
Siplivaia
L E
LE
Karpenko
E N
EN
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D004910:Erythrocyte Membrane; D022781:Hepatocytes / Q000378:metabolism; D007165:Immunosuppression Therapy; D007273:Injections, Intramuscular; D015227:Lipid Peroxidation; D008747:Methylcellulose; D010592:Pharmaceutic Aids; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus; D013997:Time Factors
D004337:Drug Carriers; D010592:Pharmaceutic Aids; D004317:Doxorubicin; D008747:Methylcellulose