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Heba F. Salem Rasha M. Kharshoum Lekaa F. Abdel Hakim Mohamed E. Abdelrahim 《Journal of liposome research》2016,26(4):324-335
Purpose: Voriconazole has both low aqueous solubility and stability. We hypothesize that designing voriconazole in the form of a nano powder inhaler at a geometric diameter within 1–5?μm will enhance its stability and solubility. Therefore, we prepared nanoagglomerates of voriconazole which will collapse in the lungs to reform the nanoparticles.Method: The nanoparticles were formulated using both stearic acid and sodium deoxycholate as edge activators. Osmogenic polycation polyethyleneimine (PEI) was used to form agglomerates of controllable size.Results: Voriconazole nanoparticles and agglomerates showed a significant higher cumulative drug release than the pure powder (p?0.05) with R2?=?0.95. Small-sized particles were formed (353?nm), while their zeta potential was ?30.7?mV. The agglomerates were 2.7?μm in size and their zeta potential was ?20.9?mV. The formation of porous agglomerates was confirmed using a transmission electron microscope. Cascade impactor was used to evaluate the aerodynamic properties of the nanoparticles and the agglomerates. The aerodynamic characterization of the nanoparticles and the agglomerates resulted in a significant smaller mass median aerodynamic diameter (MMAD) (p?0.05) and higher fine particle dose (FPD) (p?0.01), fine particle fraction (FPF) (p?0.01), and total emitted dose (TED) (p?0.01) than the pure powder.Conclusion: The results suggest that using the combination of edge activators and diluted polycationic polymer solution provides porous voriconazole nanoagglomerates in a respirable range, which is proved successful in enhancing both the deposition and the dissolution of water insoluble-drugs in the lung. 相似文献
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The bronchial flow is approximately 1% of the total pulmonary flow. Anastomosis between the bronchial and pulmonary vessels occurs primarily at the microcirculatory level. It is assumed that bronchopulmonary anastomoses are present in a homogeneous manner throughout lung parenchyma. To investigate this issue, an in situ blood-perfused left lower lung lobe (500 ml/min) was prepared in a live dog. The bronchial flow rate in the entire lobe was monitored using the rate of volume gain in the reservoir while the pulmonary and bronchial flow in the subpleural region was monitored using laser-Doppler flowmetry. The results were expressed as ratio of bronchial to pulmonary flow rate for the entire lobe and for the subpleural region. We found that, for the entire lobe, bronchial flow was 1.0% of pulmonary flow, while for the subpleural region this ratio was much higher, with an average of 12%. In two different experimental conditions that were imposed to affect the global bronchial flow, these ratios changed in the same direction as the global bronchial flow. After transfusion of blood into the animal, bronchial flow increased to 1.7%, while the subpleural bronchial flow increased to 18% of the subpleural pulmonary flow. During elevation of venous pressure, bronchial flow decreased to 0.6%, while the subpleural bronchial flow decreased to 10% of the subpleural pulmonary flow. The differences in the ratios between the global and subpleural region may be explained by having low pulmonary blood flow in the periphery compared with the interior regions of the lung.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献