Evaluation of Brain Targeting in Rats of Xiongbing Microemulsion Nasal Delivery by the Microdialysis Technique

OBJECTIVE To evaluate the brain targeting of intranansal administration Xiongbing microemulsion and investigate its feasibility by the representative constituent of tetramethylpyrazine(TMP).METHODS Blood and striatum dialysate samples were continuously collected by blood and brain microdialysis technique in rats after intragastric(ig),intravenous(iv) and intranansal(in) administration.The concentration of TMP in dialysate samples were measured by HPLC,the pharmacokinetic parameters were calculated by pharmacokinetic software DAS2.1,and evaluated the brain targeting by the value of drug targeting index(DTI).RESULTS The measured pharmacokinetics of free TMP concentration in blood and brain all fited single compartment model after intragastric administration,and two-compartment model after intranansal and intravenous administration.The absolute bioavailability(F) of intragastric administration was(41.89±5.16)%,t1/2 and MRT0-∞ of TMP in brain was approximate compared with intranansal administration,but the cmax and AUC0-∞ was significantly lesser than its.The F of intranansal administration was(86.60±2.02)%,and AUC0-∞ in brain was approximate to intravenous administration,but the t1/2 and MRT0-∞ was significantly prolonged,and increased by nearly 1.16,1.24 respectively.Its DTI value was 1.07.CONCLUSION The AUC0-∞ values of TMP in brain were approximate between intravenous and intranansal administration,part of TMP could be straight transported into brain by intranansal administration,which could improve the brain targeting of Xiongbing Microemulsion,and showed a prolonged duration of TMP concentration in the brain.Therefor,intranansal administration of Xiongbing Microemulsion could be a promising alternative to traditional administration routes.