Saturated Fatty Acid Emulsions Open the Blood-Brain Barrier and Promote Drug Delivery in Rat Brains.

ABSTRACT

We performed this study to evaluate whether saturated fatty acid (SFA) emulsions affect the BBB and determine the duration of BBB opening, thereby promoting drug delivery to the brain. Butyric, valeric, caproic, enanthic, and caprylic acid emulsions were infused into the carotid artery of the rat model. We evaluated the BBB opening and drug delivery over time. The trypan blue and doxorubicin delivery studies were repeated from 30 min to 6 h. In the 1 h rats in each group, transmission electron microscopy (TEM) was performed to morphologically evaluate tight junctions, and the delivery of temozolomide was assessed by desorption electrospray ionization mass spectrometry. The ipsilateral hemisphere was positive for trypan blue staining in all the five SFA emulsion groups. In the valeric, enanthic, and caprylic acid emulsion groups, RGB ratios were significantly higher at 30 min and decreased thereafter. Doxorubicin delivery increased in all emulsion groups at all time points. Tight junctions were observed to be open in all groups. TMZ delivery was significantly higher in the ipsilateral hemisphere. In conclusion, intra-arterially infused SFA emulsions opened the BBB and promoted drug delivery within 30 min, which decreased thereafter. Therefore, SFA emulsions may aid BBB research and promote drug delivery to the brain.