OBJECTIVE To investigate the in vitro and in vivo potential of formulated valproic acid-encapsulated nanoemulsion in terms of drug penetrability across the blood-brain barrier. METHODS Human cerebral microvascular end...OBJECTIVE To investigate the in vitro and in vivo potential of formulated valproic acid-encapsulated nanoemulsion in terms of drug penetrability across the blood-brain barrier. METHODS Human cerebral microvascular endothelial cells(hCMEC/D3)and human cortical astrocytes(SC-1800)were cultured on the membrane of the transwell inserts as to build the co-culture model of in vitro BBB model.Drug penetration analysis was then conducted at various time intervals for 24 h.The in vivostudy of this formulated nanoemulsion was also investigated using Sprague Dawley rats.They were treated with VANE 60mg·kg-1 or valproic acid 60mg·kg-1 via intraperitoneal route before being anesthetized and sacrificed by cardiac puncture at different time points after administration.The blood and brain were collected and processed.The samples were analyzed with HPLC to determine the pharmacokinetic profile and biodistribution of the drug in the brain.RESULTS The formulated VANE had apparent permeability coefficient of 0.205cm·s-1 in vitro studies.It was 1.06-fold better than the drug solution.It showed that the VANE can penetrate across the BBB faster than the drug solution.The cumulative amount was reported to be 1.12-fold higher that the drug solution.This briefly suggests the VANE can be good candidate to promote the uptake of drug into the brain.In in vivo study,the formulated nanoemulsion showed remarkably improved pharmacokinetic parameters with 3.85-fold higher of total area under the curve-time curve(AUC)and 2.81-fold higher in maximum concentration of drug in blood plasma(cmax).More interestingly,the half-life(T1/2)is prolonged by 1.80-fold and its clearance(Cl)was reduced by 3.85-fold.CONCLUSION The formulated nanoemulsions were able to improve most of the pharmacokinetic parameter thus this formulation technique improves the bioavailability of the drug in the brain compared to the drug solution alone.展开更多
文摘OBJECTIVE To investigate the in vitro and in vivo potential of formulated valproic acid-encapsulated nanoemulsion in terms of drug penetrability across the blood-brain barrier. METHODS Human cerebral microvascular endothelial cells(hCMEC/D3)and human cortical astrocytes(SC-1800)were cultured on the membrane of the transwell inserts as to build the co-culture model of in vitro BBB model.Drug penetration analysis was then conducted at various time intervals for 24 h.The in vivostudy of this formulated nanoemulsion was also investigated using Sprague Dawley rats.They were treated with VANE 60mg·kg-1 or valproic acid 60mg·kg-1 via intraperitoneal route before being anesthetized and sacrificed by cardiac puncture at different time points after administration.The blood and brain were collected and processed.The samples were analyzed with HPLC to determine the pharmacokinetic profile and biodistribution of the drug in the brain.RESULTS The formulated VANE had apparent permeability coefficient of 0.205cm·s-1 in vitro studies.It was 1.06-fold better than the drug solution.It showed that the VANE can penetrate across the BBB faster than the drug solution.The cumulative amount was reported to be 1.12-fold higher that the drug solution.This briefly suggests the VANE can be good candidate to promote the uptake of drug into the brain.In in vivo study,the formulated nanoemulsion showed remarkably improved pharmacokinetic parameters with 3.85-fold higher of total area under the curve-time curve(AUC)and 2.81-fold higher in maximum concentration of drug in blood plasma(cmax).More interestingly,the half-life(T1/2)is prolonged by 1.80-fold and its clearance(Cl)was reduced by 3.85-fold.CONCLUSION The formulated nanoemulsions were able to improve most of the pharmacokinetic parameter thus this formulation technique improves the bioavailability of the drug in the brain compared to the drug solution alone.
