Saturated Fatty Acid Emulsions Open the Blood–Brain Barrier and Promote Drug Delivery in Rat Brains
Kyoung Su Sung,
Won Ho Cho,
Seung Heon Cha,
Yong-Woo Kim,
Seon Hee Choi,
Hak Jin Kim,
Mi Sook Yun
Affiliations
Kyoung Su Sung
Department of Neurosurgery, Dong-A University Hospital, Dong-A University College of Medicine, Busan 49201, Republic of Korea
Won Ho Cho
Department of Neurosurgery, Pusan National University Hospital, Biomedical Institute of Pusan National University Hospital, School of Medicine, Pusan National University, Busan 49241, Republic of Korea
Seung Heon Cha
Department of Neurosurgery, Pusan National University Hospital, Biomedical Institute of Pusan National University Hospital, School of Medicine, Pusan National University, Busan 49241, Republic of Korea
Yong-Woo Kim
Department of Radiology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
Seon Hee Choi
Institute for Research and Industry Cooperation, Pusan National University, Busan 49241, Republic of Korea
Hak Jin Kim
Department of Radiology, Pusan National University Hospital, Biomedical Institute of Pusan National University Hospital, School of Medicine, Pusan National University, Busan 49241, Republic of Korea
Mi Sook Yun
Division of Biostatistics, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
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.
