Effect of polysorbate 80 on the intranasal absorption and brain distribution of tetramethylpyrazine phosphate in rats.

Drug delivery to the brain is limited by the blood-brain barrier (BBB). Intranasal delivery is a non-invasive route of drug administration which can bypass the BBB and contributed to a direct and rapid transport of drugs to the brain. However, intrinsic drug distribution to the brain after intranasal administration may not be sufficient to achieve required clinical efficacy. In this study, taking 2,3,5,6-tetramethylpyrazine (TMPP) as a model drug, the feasibility of using polysorbate 80 as an absorption enhancer and message guider to increase drug distribution in the brain was employed. After intravenous/intranasal administration of TMPP formulations with/without polysorbate 80, drug concentration in both plasma and brain was measured at specific time points, and the pharmacokinetic parameters were compared. It was demonstrated that compared with intravenous administration, brain targeting efficiency of TMPP was improved remarkably by intranasal route. Upon intranasal administration, the addition of polysorbate 80 significantly increased TMPP concentration in both plasma and brain linearly up to polysorbate 80 concentration 2%. Based on drug targeting efficiency, drug targeting index, and nose-to-brain direct transport percentage, polysorbate 80 decreased the nose-to-brain direct transport ratio of TMPP in a polysorbate 80 concentration-dependent manner although the total brain targeting efficiency was unchanged, with significantly enhanced absolute drug concentration in the brain achieved. In summary, polysorbate 80 is a promising excipient to increase drug concentration in both plasma and brain via intranasal route.