THEME: "Frontiers in Nanomedicine and Advanced Drug Delivery Systems"
Pusan National University, South Korea
Unsaturated free fatty acid emulsion infusion into carotid artery enhances drug delivery to the rat brain
TBA
Aims. To determine whether the
BBB opens to enhance drug delivery during the acute stage of unsaturated fat
embolism.
Methods.
We infused oleic, linoleic,
and linolenic acid emulsions through the right common carotid
artery of rats, followed by trypan blue for gross and lanthanum for electron
microscopic (EM) examination.
Doxorubicin and temozolomide were also administered, and then the
rats were euthanized at 30 min, 1 h, and 2 h. Trypan blue hue was analyzed to
semiquantitatively measure BBB opening. Desorption
electrospray ionization-mass spectrometry (DESI-MS) imaging was used to
evaluate drug delivery.
Results.
Trypan blue staining observed in each group 30 min after emulsion infusion
increased at 1 h and decreased after 2 h in the oleic acid group. The linoleic
and linolenic acid groups showed weak staining over time. The hue and trypan
blue analysis results were corroborative. EM showed tight junction opening, whereas
DESI-MS imaging showed increased doxorubicin and temozolomide signal
intensities in ipsilateral
hemispheres of all three groups.
Conclusion. We
demonstrated that oleic, linoleic,
and linolenic acid emulsions opened the BBB, promoting drug
delivery to the brain. Hue
analysis and DESI-MS imaging are appropriate for analysis of doxorubicin and
temozolomide concentrations in brain tissue