ABSTRACT
OBJECTIVE: Using RGD10-NGR9 dual-targeting superparamagnetic iron oxide nanoparticles to evaluate their potential value in tumor angiogenesis magnetic resonance imaging (MRI) and the biodistribution in vitro and in vivo. MATERIALS AND METHODS: Dual-targeting RGD10-NGR9 ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were designed and synthesized in our previous study. In vitro, prussian blue staining and phenanthroline colorimetry were conducted to evaluate binding affinity and adsorption of dual-targeting USPIO nanoparticles to αvß3-integrin/APN positive cells. In vivo, a xenograft mouse tumor model was used to evaluate the potential of the dual-targeting nanoparticles as an MRI contrast agent. After intravenous injection, the contrast-to-noise ratio (CNR) values of MR images obtained were calculated at predetermined time-points. The iron level was detected to access the biodistribution and plasma half-time. RESULTS: In vitro, dual-targeting USPIO nanoparticles bound to proliferating human umbilical vein endothelia cells with high specificity. In vivo, contrast MRI of xenograft mice using dual-targeting nanoparticles demonstrated a significant decrease in signal intensity and a greater increase in CNR than standard MRI and facilitated the imaging of tumor angiogenesis in T2*WI. In terms of biodistribution, dual-targeting USPIO nanoparticles increased to 1.83 times in tumor lesions as compared to the control. And the plasma half-time was about 6.2 h. CONCLUSION: A novel RGD10-NGR9 dual-targeting USPIO has a great potential value as a contrast agent for the identification of tumor angiogenesis on MRI, according to the high specific affinity in vitro and in vivo.
Subject(s)
Contrast Media/pharmacokinetics , Dextrans/pharmacokinetics , Magnetic Resonance Imaging/methods , Neoplasms, Experimental/diagnostic imaging , Neovascularization, Pathologic/diagnostic imaging , A549 Cells , Animals , Dextrans/chemistry , Heterografts , Humans , Magnetite Nanoparticles/chemistry , Mice , Mice, Inbred BALB C , Mice, Nude , Peptides , Tissue DistributionABSTRACT
Capillary electrophoresis (CE) provides high separation efficiency and thus is suitable for the analysis of complex mixtures of structurally similar compounds. The versatile nature of CE can be realised by controlling the chemistry of the inner capillary wall, by modifying the electrolyte composition and by altering the physicochemical properties of the analyte. A CE method has been developed for the separation of three macrolide antibiotics, erythromycin, oleandomycin and josamycin. A systematic approach was used to maximise analyte differential electrophoretic mobility by manipulating electrolyte pH, molarity and composition. In addition, some instrumental parameters such as capillary length and diameter and applied voltage were varied. The effect of the sample solvent and on-capillary concentrating techniques such as field amplified sample injection were investigated. Also, the influence of the injection of a water plug on the quantity of sample injected was demonstrated. The macrolides were completely resolved in less than 30 min in a 100 cm x 75 microm I.D. fused-silica uncoated capillary with a Z-shaped flow cell of path-length 3 mm. The analysis was performed in a 75 mM phosphate buffer (pH 7.5) with 50% (v/v) methanol and an applied voltage of 25 kV was selected to effect the separation.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Electrophoresis, Capillary/methods , Erythromycin/isolation & purification , Josamycin/isolation & purification , Oleandomycin/isolation & purification , Chemical Phenomena , Chemistry, Physical , Electrolytes , Electrophoresis, Capillary/instrumentation , Hydrogen-Ion Concentration , Osmolar Concentration , SolventsABSTRACT
Current compendial methods of assay for the analysis of erythromycin and its related substances involve the use of microbiological techniques. These techniques are non-selective and tedious, thus there is a need for the development of highly specific, quantitative analytical methods. Erythromycin was analysed in a 50 mM phosphate buffer (pH 7.5) and run at an applied voltage of 20 kV. Detection sensitivity was enhanced by using a wavelength of 200 nm and selecting an injection solvent of lower conductivity than the electrolyte: acetonitrile-water (20:80, v/v). In order to facilitate the separation of erythromycin and its related substances, the organic solvent ethanol (35%, v/v) was incorporated into a modified 150 mM phosphate buffer (pH 7.5) and run at an applied voltage of 30 kV. Resolution of all the compounds was achieved in approximately 45 min. The methods described are accurate and precise and thus suitable for the quantitative determination of erythromycin and the related substances, erythromycin C, anhydroerythromycin and N-demethylerythromycin A.
