Intraocular administration of tetramethylpyrazine hydrochloride to rats: a direct delivery pathway for brain targeting?

Abstract

The purpose of this study was to compare the pharmacokinetic profile of tetramethylpyrazine hydrochloride (TMPH) in rat plasma and tissues following intravenous (iv), intragastric (ig) and intraocular (io) administration. After io, ig and iv administration of a single dose at 10 mg/kg, tissue and plasma samples drawn from the femoral artery were collected at timed intervals. The concentration of TMPH in the samples was analyzed using high-performance liquid chromatography (HPLC). The area under the concentration–time curve ( AUC ) and the drug targeting efficiency percentage ( DTE (%)) were calculated to evaluate the targeting efficiency of the drug with the three different administration routes. After io administration, TMPH was rapidly absorbed to reach its peak plasma and brain concentration within 5 min. The systemic bioavailability obtained with io administration was greater than that obtained through the ig route (63.22% vs. 16.88%). The AUC t rank order of the iv administration group was AUC kidney > AUC heart > AUC liver > AUC brain > AUC spleen > AUC lung ; that of the ig administration group as AUC kidney > AUC liver > AUC heart > AUC spleen > AUC brain > AUC lung ; while that of the io administration group was AUC kidney > AUC brain > AUC heart > AUC liver > AUC spleen > AUC lung . The ratio of the AUC brain value between the io route and iv injection was 1.05, which was greater than that obtained after ig administration (0.30). The DTE after io administration was calculated: brain (165.72%), heart (97.76%), liver (113.06%), spleen (105.31%), lung (163.40%) and kidney (135.31%). The io administration group showed obvious drug transport to the brain. These results indicate that TMPH is rapidly absorbed from the eye into the systemic circulation, and there may be a direct translocation pathway for TMPH from the eye to the brain. Therefore, io administration of TMPH could be a promising alternative to intravenous and oral approaches.

The protective effects of ligustrazine on ischemic stroke: a systematic review and meta-analysis of preclinical evidence and possible mechanisms

“…Previous research has demonstrated that ligustrazine has the ability to penetrate the BBB and distribute across various brain regions ( Tsai and Liang, 2001 ). However, its biological half-life when taken orally is limited to 0.5–2 h. Utilizing ligustrazine - loaded liposomes ( Xia et al, 2016 ), transdermal administration drugs ( Qi et al, 2002 ), intranasal administration ( Feng et al, 2009 ), and intraocular administration ( Mao et al, 2019 ) can enhance the efficiency of ligustrazine in crossing the BBB and reaching the brain. Moreover, ligustrazine exhibits protective effects against CIS damage by reducing BBB permeability ( Tan et al, 2015 ; Jin et al, 2021 ), possibly through the inhibition of the JAK/STAT signaling pathway ( Gong et al, 2019 ) and the reduction of MMP-9 levels ( Jin et al, 2021 ).…”