Preparation Of Oxygen-laden Emulsions And Study On Their Application Of Reoxygenation

Humen bodys’oxygen using processes can be divided into the four stages:oxygen inhalation,gas exchange,circulation in vivo and oxygen consumption in tissue.The blockage of any abovementioned stages could cause human hypoxia,which lead to tissue metabolism abnormalities.This thesis aims at improving lung ventilation via pulmonary administration to ease the hyoxemia which may be caused by blockage of the stages of oxygen inhalation and gas exchange.In this thesis,perfluorocarbon was employed as an oxygen carrier,combined with two different pulmonary delivery carriers to prepare two kinds of artificial oxygen carrier for pulmonary administration.The specific contents are as follows:1、PLGA-PEG/PFOB emulsion was prepared using PLGA-PEG as a carrier.Cell hypoxia-reoxygenation experiment reveals that cell viability has a significant enhancement after reoxygenation with PLGA-PEG/PFOB emulsion because of the sufficient and timely oxygen supply.Meanwhile,the change of the expression level of HIF-1αis similar to cell viability during reoxygenation,which suggest HIF-1αor its downstream proteins may make a significant contribution to cell viability.In vivo oxygen supply was assessed in rats through pulmonary delivery,which shows that PLGA-PEG/PFOB emulsion can supply oxygen to rats and improve rats’lungs ventilation.2、Artificial pulmonary surfactant was prepared with DPPC as the main ingredient,and then combined with PFOB,DPPC/PFOB emulsion was prepared.Cell hypoxia-reoxygenation experiment shows that cell viability can recover rapidly after reoxygenation with DPPC/PFOB emulsion.Then the emulsion was incubated with A549 cells to investigate its influence to cell growth under different oxygen concentration.This experiment found that when oxygen concentration is low,DPPC/PFOB emulsion can promote growth of A549 cells,which indicate that the emulsion has the capacity to supply oxygen to cells.Meanwhile,after co-incubation under 1%oxygen concentration,the content of intracellular HIF-1αalso appeared a significantly increase,which play a protective role in cells.Finally,we established rabbit models about sea drowning and acute respiratory distress syndrome（ARDS）to investigate the effect of DPPC/PFOB emulsion on improving animal lung ventilation,which proved that the emulsion can significantly improve lung ventilation and enhance partial pressure of oxygen（PO₂）after rabbits inhaled the emulsion.In conclusion,all resuls prove that PLGA-PEG/PFOB emulsions and DPPC/PFOB emulsions have the capacity to supply oxygen to cells and improve lung ventilation after pulmonary delivery.The emulsions may have great potential applications in the field of alleviate hypoxemia in the future.