Assessment of the Blood-Brain Barrier Permeability of Potential Neuroprotective Aurones in Parallel Artificial Membrane Permeability Assay and Porcine Brain Endothelial Cell Models

作者：Liew Kok Fui; Hanapi Nur Aziah; Chan Kit Lam; Yusof Siti R; Lee Chong Yew^*

来源：Journal of Pharmaceutical Sciences, 2017, 106(2): 502-510.

DOI：10.1016/j.xphs.2016.10.006

• blood-brain barrier
• permeability
• in vitro models
• CNS
• drug-like properties
• drug design

Previously, several aurone derivatives were identified with promising neuroprotective activities. In developing these compounds to target the central nervous system ( CNS), an assessment of their blood-brain barrier ( BBB) permeability was performed using in vitro BBB models: parallel artificial membrane permeability assay-BBB which measures passive permeability and primary porcine brain endothelial cell model which enables determination of the involvement of active transport mechanism. Parallel artificial membrane permeability assay-BBB identified most compounds with high passive permeability, with 3 aurones having exceptional P-e values highlighting the importance of basic amine moieties and optimal lipophilicity for good passive permeability. Bidirectional permeability assays with porcine brain endothelial cell showed a significant net influx permeation of the aurones indicating a facilitated uptake mechanism in contrast to donepezil, a CNS drug included in the evaluation which only displayed passive permeation. From pH-dependent permeability assay coupled with data analysis using pCEL-X software, intrinsic transcellular permeability ( P-o) of a representative aurone 4-3 was determined, considering factors such as the aqueous boundary layer that may hinder accurate in vitro to in vivo correlation. The P-o value determined supported the in vivo feasibility of the aurone as a CNS-active compound.

• 出版日期2017-2