Measurement of drug and macromolecule diffusion across atherosclerotic rabbit aorta ex vivo by attenuated total reflection-Fourier transform infrared imaging.
Diffusion of two model drugs-benzyl nicotinate and ibuprofen-and the plasma macromolecule albumin across atherosclerotic rabbit aorta was studied ex vivo by attenuated total reflection-Fourier transform infrared (ATR-FTIR) imaging. Solutions of these molecules were applied to the endothelial surface of histological sections of the aortic wall that were sandwiched between two impermeable surfaces. An array of spectra, each corresponding to a specific location in the section, was obtained at various times during solute diffusion into the wall and revealed the distribution of the solutes within the tissue. Benzyl nicotinate in Ringer's solution showed higher affinity for atherosclerotic plaque than for apparently healthy tissue. Transmural concentration profiles for albumin demonstrated its permeation across the section and were consistent with a relatively low distribution volume for the macromolecule in the middle of the wall. The ability of albumin to act as a drug carrier for ibuprofen, otherwise undetected within the tissue, was demonstrated by multivariate subtraction image analysis. In conclusion, ATR-FTIR imaging can be used to study transport processes in tissue samples with high spatial and temporal resolution and without the need to label the solutes under study.
Palombo
Francesca
F
Imperial College London, Department of Chemical Engineering and Chemical Technology, South Kensington Campus, London, SW7 2AZ, United Kingdom.
Danoux
Charlène B
CB
Weinberg
Peter D
PD
Kazarian
Sergei G
SG
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001018:Aortic Diseases / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism*; D001774:Blood Chemical Analysis / Q000379:methods; D004058:Diffusion; D007052:Ibuprofen / Q000493:pharmacokinetics*; D009539:Nicotinic Acids / Q000493:pharmacokinetics*; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*
D009539:Nicotinic Acids; C025653:nicotinic acid benzyl ester; D007052:Ibuprofen