ABSTRACT
This study is to evaluate the sustained-release effect of the thermosensitive in situ gel for injection of boanmycin hydrochloride (BAM) by bioluminescence imaging in nude mice. BAM was labeled with fluorescein isothiocyanate (FITC). The FITC-labeled BAM (FITC-BAM) was purified by dialysis and Sephadex G25 gel column, and then was identified by matrix-assisted laser desorption ionization/time of flight (MALDI-TOF). The model of experimental hepatoma HepG-2 nude mice was established, and the optical imaging system was applied to evaluate the distribution of FITC-BAM in vivo. Results of MALDI-TOF proved that the major molecular ratio of BAM : FITC was 1 : 1 or 1 : 2. Bioluminescence imaging showed that the diffusion of FITC-BAM in situ gel group was significantly delayed compared with the negative control group. This study demonstrated that the thermosensitive in situ gel can effectively delay the release of boanmycin hydrochloride, and extend the retention time in vivo.
Subject(s)
Animals , Female , Humans , Mice , Antibiotics, Antineoplastic , Chemistry , Pharmacokinetics , Bleomycin , Chemistry , Pharmacokinetics , Delayed-Action Preparations , Drug Carriers , Chemistry , Fluorescein-5-isothiocyanate , Chemistry , Pharmacokinetics , Gels , Chemistry , Hep G2 Cells , Injections , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Temperature , Tissue Distribution , ViscosityABSTRACT
Poloxamer F127, poloxamer F68 and hydroxypropyl methylcellulose K4M were used to prepare the thermosensitive in situ gel of boanmycin hydrochloride for injection. Its gelation temperature, rheological behavior, texture characteristics, scanning electron microscopy, in vitro and in vivo drug release were evaluated. These results showed that the formulation was a fluid solution at room temperature, which could become semisolid at the temperature of 37 degrees C, and the thermally induced sol-gel transition allowed to be injectable and in situ setting. The formulation was constructed into a tridimensional network at gelation temperature. The drug release was controlled by the diffusion of the drug and the erosion of the gelmatrix. The pharmacokinetics indicated that the drug could be released slowly for up to 48 hours after subcutaneous administration in rats.
Subject(s)
Animals , Male , Rats , Antibiotics, Antineoplastic , Pharmacokinetics , Bleomycin , Pharmacokinetics , Diffusion , Drug Delivery Systems , Gels , Hypromellose Derivatives , Injections, Subcutaneous , Methylcellulose , Chemistry , Microscopy, Electron, Scanning , Poloxamer , Chemistry , Rats, Sprague-Dawley , Rheology , Temperature , ViscosityABSTRACT
Cellular senescence is one of the important steps against tumor. This study was to observe the characteristics of boningmycin induced senescence of human tumor cells. MIT method and clone formation assay were used to detect the growth-inhibitory effect. Cellular senescence was detected with senescence-associated beta-galactosidase staining. Cell cycle distribution and accumulation of intracellular reactive oxygen species (ROS) were analyzed with flow cytometry. Protein expression was detected by Western blotting. The results showed that the growth-inhibitory effect of boningmycin was obviously stronger on human oral epithelial carcinoma KB cells than that on non-small cell lung cancer A549 cells. Comparison to the similar action of doxorubicin, that boningmycin induced the features of cellular senescence in both cell lines, its due to the arrest at G2/M phase and an increase of ROS level. The molecular senescence marker P21 increased significantly after boningmycin treatment at a dosage of 0.1 micromol x L(-1), whereas a higher concentration of it induced apoptosis. The results indicated that cellular senescence induced by boningmycin was one of its mechanisms in tumor suppression.
Subject(s)
Humans , Antibiotics, Antineoplastic , Pharmacology , Apoptosis , Bleomycin , Pharmacology , Carcinoma, Non-Small-Cell Lung , Metabolism , Pathology , Cell Cycle , Cell Proliferation , Cellular Senescence , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Dose-Response Relationship, Drug , Doxorubicin , Pharmacology , KB Cells , Lung Neoplasms , Metabolism , Pathology , Poly(ADP-ribose) Polymerases , Metabolism , Reactive Oxygen Species , Metabolism , Tumor Suppressor Protein p53 , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm.</p><p><b>METHODS</b>Micro-dilution method was used to determine the minimal inhibitory concentrations (MICs) of sansanmycin, gentamycin, carbenicillin, polymyxin B, roxithromycin, piperacillin, and tazobactam. PA1 and PA27853 biofilms were observed under optical microscope after staining and under SEM after treatment with sansanmycin at different dosages and combined treatment with sansanmycin and roxithromycin. Viable bacteria in PA1 and PA27853 biofilms were counted after treatment with sansanmycin at different dosages or combined treatment with sansanmycin and roxithromycin.</p><p><b>RESULTS</b>The MIC of sansanmycin was lower than that of gentamycin and polymyxin B, but was higher than that of carbenicillin. Roxithromycin enhanced the penetration of sansanmycin to PA1 and PA27853 strains through biofilms. PA1 and PA27853 biofilms were gradually cleared with the increased dosages of sansanmycin or with the combined sansanmycin and roxithromycin.</p><p><b>CONCLUSION</b>Sub-MIC levels of roxithromycin and sansanmycin substantially inhibit the generation of biofilms and proliferation of bacteria. Therefore, combined antibiotics can be used in treatment of intractable bacterial infection.</p>