School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
Drug Deliv Transl Res. 2019 Feb;9(1):311-318. doi: 10.1007/s13346-018-0580-y.
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.
药物向脑部的递送受到血脑屏障（BBB）的限制。鼻内给药是一种非侵入性的药物给药途径，可绕过 BBB，并有助于药物直接快速地输送到大脑。然而，鼻内给药后内在向大脑的药物分布可能不足以达到所需的临床疗效。在这项研究中，以 2,3,5,6-四甲基吡嗪（TMPP）为模型药物，研究了聚山梨酯 80 作为吸收增强剂和信息引导剂来增加药物在大脑中的分布的可行性。在静脉/鼻内给予 TMPP 制剂有/没有聚山梨酯 80 后，在特定时间点测量血浆和大脑中的药物浓度，并比较药代动力学参数。结果表明，与静脉给药相比，TMPP 通过鼻内途径显著提高了脑靶向效率。鼻内给药时，聚山梨酯 80 的添加可使 TMPP 的浓度在血浆和大脑中呈线性增加，直至聚山梨酯 80 的浓度达到 2%。基于药物靶向效率、药物靶向指数和鼻内直接转运率，聚山梨酯 80 以聚山梨酯 80 浓度依赖性方式降低了 TMPP 的鼻内直接转运比，尽管总脑靶向效率保持不变，但大脑中的绝对药物浓度显著增加。总之，聚山梨酯 80 是一种有前途的赋形剂，可通过鼻内途径增加血浆和大脑中的药物浓度。
