ABSTRACT
We present data on pharmacokinetics of free and liposomal forms of gentamicin. Comparative study of two drug forms showed that immobilization of gentamicin in liposomes significantly increased most important pharmacokinetic parameters of the antibiotic (AUC, Cmax, MRTpo, T(1/2), Kel, Vzpo) and reduced Clpo and Kel.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Gentamicins/pharmacokinetics , Liposomes/metabolism , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Gentamicins/administration & dosage , Gentamicins/pharmacology , Injections, Intraperitoneal , Iodine Radioisotopes/metabolism , Lipid Peroxidation/drug effects , Liposomes/ultrastructure , Mice , Microscopy, Electron , Spectrophotometry , Time FactorsABSTRACT
Glanders is a zoonotic infection inducing acute forms of the disease (pneumonia, sepsis) in humans and animals under certain conditions, which even with the use of modern chemotherapy have unfavourable prognosis. Insufficient of efficacy of antibiotics with in vitro low MIC for planktonic bacterial suspension of Burkholderia mallei in chemotherapy of acute forms of glanders was due to the capacity of the pathogen for intracellular survival and formation of biofilms. Under such conditions the susceptibility of B. mallei to antibiotics lowered by several orders of magnitude. Chemotherapy of the glanders acute forms in animals usually provided only an increase of the lifespan, while among the survivors there was recorded a high relapse rate. More favourable outcomes were observed with the use of in vitro effective antibiotics in the form of clathrate compounds or especially liposomal forms. In the experiments with golden hamsters the survival rate reached 100% in 1000 Dlm infection even with the treatment onset by meropenem liposomal form 48 hours after the infection. Chemotherapeutics in the liposomal form significantly lowered resistance of B. mallei in both the experiments with a suspension of planktonic organisms and the use of bacteria interned in eukaryotic cells (Tetrahymena pyriformis).
Subject(s)
Anti-Bacterial Agents/pharmacology , Burkholderia mallei/drug effects , Glanders/drug therapy , Thienamycins/pharmacology , Acute Disease , Animals , Burkholderia mallei/pathogenicity , Ceftazidime/pharmacology , Cricetinae , Doxycycline/pharmacology , Female , Fever/drug therapy , Glanders/etiology , Glanders/microbiology , Glanders/mortality , Liposomes , Male , Meropenem , Mesocricetus , Microbial Sensitivity Tests , Survival Rate , Terpenes/chemistry , Terpenes/pharmacologyABSTRACT
A new method for obtaining the liposomal formulation of streptomycin and tetracycline is described in the present work. The physicochemical properties of this formulation were evaluated. We compared the effects of free and liposomal formulations from streptomycin and tetracycline on activity of liver enzymes in albino mice. Immobilization of antibiotics in liposomes was followed by a decrease in the inhibitory effect on protease, alkaline phosphatase, and phosphorylase. The influence of this preparation on ATPase was reduced by 2 times.
Subject(s)
Alkaline Phosphatase/metabolism , Liposomes/metabolism , Liver/enzymology , Phosphorylases/metabolism , Protease Inhibitors/metabolism , Streptomycin/pharmacology , Tetracycline/pharmacology , Alkaline Phosphatase/antagonists & inhibitors , Animals , Liver/drug effects , Mice , Phosphorylases/antagonists & inhibitorsABSTRACT
Preparation and physicochemical properties of liposome-incorporated tetracycline are described. Comparison of the effects of tetracycline hydrochloride in free and liposome-incorporated forms on enzymatic functions of the liver showed that immobilization of the antibiotic into liposomes protects liver cells from functional disturbances.
Subject(s)
Liver/drug effects , Liver/enzymology , Tetracycline/pharmacology , Adenosine Triphosphatases/metabolism , Alkaline Phosphatase/metabolism , Animals , Animals, Outbred Strains , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Liposomes , Liver Extracts/metabolism , Liver Function Tests , Mice , Phosphorylases/metabolism , Tetracycline/administration & dosage , Time FactorsABSTRACT
The data on preparation of liposome-entrapped gentamicin sulfate and cefoperazone and their investigation on albino mice with staphylococcal destructive pneumonia are presented. Comparative study of the efficacy of gentamicin sulfate and cefoperazone in free and liposome-entrapped forms showed that immobilization of the antibiotics in phospholipid vesicles provided a 2-fold increase of their efficacy.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Cefoperazone/administration & dosage , Gentamicins/administration & dosage , Pneumonia, Staphylococcal/drug therapy , Animals , Anti-Bacterial Agents/therapeutic use , Cefoperazone/therapeutic use , Female , Gentamicins/therapeutic use , Liposomes , Male , Mice , Mice, Inbred StrainsABSTRACT
An in vivo comparative study on penetration of free gentamicin sulfate and liposome-entrapped gentamicin sulfate to macrophages was performed and the efficacy of the treatment of destructive pneumonia was estimated on albino mice. The liposome-entrapped antibiotic was arrested by the cells of the mononuclear phagocytic system thus providing higher concentrations of the drug in the organs with high counts of macrophages, the antibiotic retention time in the organs being longer than that after the use of free gentamicin. The use of liposome-entrapped gentamicin in the treatment of destructive pneumonia made it possible to increase the host protection from 17 to 50 per cent.
Subject(s)
Gentamicins/administration & dosage , Macrophages, Peritoneal/drug effects , Pneumonia, Staphylococcal/drug therapy , Absorption , Animals , Cell Membrane Permeability , Drug Carriers , Gentamicins/pharmacokinetics , Liposomes , Macrophages, Peritoneal/metabolism , Mice , Treatment OutcomeABSTRACT
The results of studies on the incorporation of a number of antibiotics into liposomes and the use of gamma irradiation for sterilization of phospholipid vesicles are presented. The toxicity of hydrochloride tetracyclin in free and liposomal forms is estimated for golden hamster with different methods of administration.
