Study On Behavior Of Different Surface Charge Nanoparticles Through The Extravascular Fluid Transport Pathway

ObjectiveStudies have shown that interstitial fluid filled the extravascular interstitial space can flow along tunica adventitia for a long distance,composing an extravascular transport pathway for interstitial fluid.To observe the transport behavior of ferrosoferric oxide nanoparticles with different surface charges in the extravascular fluid transport pathway using magnetic resonance imaging,and to investigate the effect of surface charge on the transport behavior of nanoparticles in the extravascular fluid transport pathway.Materials and MethodsSixteen healthy male Sprague-Dawley rats aged 6-7 weeks were selected and divided into an experimental group(n=12)and a blank control group(n=4).The experimental group was further divided into electrically neutral group,positively charged group,negatively charged group,4 rats in each group.(1)Prepare ferrosoferric oxide nanoparticle solutions with different surface charges.(2)The lower extremity Taixi acupoint was used as the injection site,the magnetic resonance images of the three groups of rats in the experimental group were detected by Bruker's high magnetic field MRI small animal in vivo imaging system before and after injection.(3)The number of voxel points(volume),displacement and velocity in the signal reduction area of the experimental group after the injection were calculated and analyzed.(4)The results were verified by Prussian blue staining pathological sections.Results(1)After the injection of nanoparticles with different surface charges,the areas where the signal was significantly reduced appeared in the magnetic resonance images of the electrically neutral group,the positively charged group and the negatively charged group,and the number of voxel points in the signal reduction region increased significantly with time(P<0.01),the difference was statistically significant.(2)The speed of the signal reduction area of the electric neutral group,the positive charge group and the negative charge group showed a significant downward trend with time(P<0.01),and the speed of the signal reduction region between the three groups was significantly different(P<0.05).The average speed of the negative charge group was significantly lower than that of the electric neutral group(P<0.01)and positive charge group(P<0.05),and the difference was statistically significant.(3)The cumulative displacement of the signal-reduced areas of the electric neutral group,the positive charge group and the negative charge group showed a significant upward trend with time(P<0.01),the interaction between the experimental groups and the observation time was statistically significant(P<0.01).Over time,the cumulative displacement between experimental groups is different,and the cumulative displacement of electrically neutral group and the positive charge group was longer than the negatively charged group.(4)Prussian blue staining confirmed that the ferrosoferric oxide nanoparticles were transported in the extravascular fluid transport pathway.Conclusions(1)Ferrosoferric oxide nanoparticles with different surface charges can be transported in the extravascular fluid transport pathway.(2)The transport speed of positively charged and electrically neutral nanoparticles in the extravascular fluid transport pathway is higher than that of negatively charged nanoparticles.(3)Taking the extravascular fluid transport pathway as the route of administration not only considers the research on the mechanism of action and drug design,but also needs to pay attention to the influence of the charge on the surface of the drug carrier.