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Diffusion of Alexa Fluor 488‐Conjugated Dendrimers in Rat Aortic Tissue
Author(s) -
CHO BRENDA S.,
ROELOFS KAREN J.,
MAJOROS ISTVAN J.,
BAKER JAMES R.,
STANLEY JAMES C.,
HENKE PETER K.,
UPCHURCH GILBERT R.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1383.004
Subject(s) - alexa fluor , conjugated system , chemistry , dendrimer , biophysics , biology , fluorescence , biochemistry , physics , polymer , organic chemistry , optics
In this study, the distribution of labeled dendrimers in native and aneurysmal rat aortic tissue was examined. Adult male rats underwent infrarenal aorta perfusion with generation 5 (G5) acetylated Alexa Fluor 488‐conjugated dendrimers for varying lengths of time. In a second set of experiments, rats underwent aortic elastase perfusion followed by aortic dendrimer perfusion 7 days later. Aortic diameters were measured prior to and postelastase perfusion, and again on the day of harvest. Aortas were harvested 0, 12, or 24 h postperfusion, fixed, and mounted. Native aortas were harvested and viewed as negative controls. Aortic cross‐sections were viewed and imaged using confocal microscopy. Dendrimers were quantified (counts/high‐powered field). Results were evaluated by repeated measures ANOVA and Student's t ‐test. We found that in native aortas, dendrimers penetrated the aortic wall in all groups. For all perfusion times, fewer dendrimers were present as time between dendrimer perfusion and aortic harvest increased. Longer perfusion times resulted in increased diffusion of dendrimers throughout the aortic wall. By 24 h, the majority of the dendrimers were through the wall. Dendrimers in aneurysmal aortas, on day 0 postdendrimer perfusion, diffused farther into the aortic wall than controls. In conclusion, this study documents labeled dendrimers delivered intra‐arterially to native rat aortas in vivo , and the temporal diffusion of these molecules within the aortic wall. Increasing perfusion time and length of time prior to harvest resulted in continued dendrimer diffusion into the aortic wall. These preliminary data provide a novel mechanism whereby local inhibitory therapy may be delivered locally to aortic tissue.