DDEL-09. SATURATED FATTY ACID EMULSION OPENS THE BLOOD-BRAIN BARRIERS AND ENHANCES DRUG DELIVERY

Abstract

Abstract PURPOSE To evaluate whether saturated fatty acid (SFA) emulsion affects the BBB and whether drug delivery is promoted with the aid of SFA in the brain. MATERIAL AND METHODS Each SFA (butyric, valeric, caproic, enantic and caprylic acid) emulsion was infused into the right common carotid artery in a rat model. Trypan blue staining for qualitative and semiquantitative analysis of the BBB opening was performed. A transmission electron microscopic (TEM) exam with the contrast media for morphologic evaluation of the tight junction was obtained. Delivery of doxorubicin in the brain was determined by fluorometric analysis. Delivery of temozolomide (TMZ) through the BBB was studied by desorption electrospray ionization (DESI)-MS imaging. RESULTS The ipsilateral hemisphere revealed positive trypan blue staining in all five SFA emulsion groups. Ratios of the ipsilateral to the contralateral hemisphere of in trypan blue permeability with hue analysis was above 1.0. As the carbon number in the used SFA increased, the ratio of trypan blue permeability increased and was statistically significant (P < 0.05). The tight junction and neural interstitium were filled with the contrast media in all five SFA emulsion groups. Delivery of doxorubicin (P < 0.05) and TMZ were significantly high in the ipsilateral hemisphere compared to the contralateral hemisphere. In the caprylic acid group, the BBB opening and drug delivery were highest among the five SFA groups. CONCLUSION SFA emulsion with intraarterial infusion opened the BBB and drug delivery was enhanced consequently. Thus, SFA emulsion might be another strategy for the research of BBB opening and promotion of drug delivery in the brain.