佐米曲坦(ZT)是一种有效的第二代曲坦,通常用于缓解偏头痛发作。ZT受到各种限制;大量肝首过代谢,P-gp外排转运蛋白敏感性,和有限的(≈40%)口服生物利用度。可以探索经皮给药途径以提高其生物利用度。构建了23.31全因子设计,通过薄膜水合技术开发了24个ZT负载的畸胎瘤。药物的影响:磷脂酰胆碱比例,萜烯类型,评估了萜烯浓度和脱氧胆酸钠浓度对开发的负载ZT的萜烯的表征。粒度(PS),zeta电位(ZP),ZT截留效率(EE%),药物负载(DL%)和6h(Q6h)后的药物释放百分比是选择的因变量。进一步形态学,结晶度并进行了体内组织病理学研究,以确定最佳的畸胎体(T6)。99mTc-ZT和99mTc-ZT-T6凝胶经放射性配制用于小鼠体内生物分布研究,相对于99mTc-ZT口服液。T6节节体[包含ZT和磷脂酰胆碱(1:15),桉树脑(1%w/v)和脱氧胆酸钠(0.1%w/v)]相对于球形PS(290.2nm)是最佳的,ZP(-48.9mV),EE%(83%),DL%(3.9%)和Q6h(92.2%),可取值为0.85。通过体内组织病理学研究验证了开发的T6节膜的安全性。99mTc-ZT-T6凝胶在经皮施用后4小时显示最大脑浓度(5±0.1%ID/g),最高脑与血液比率为1.92±0.1。用99mTc-ZT-T6凝胶显着改善了ZT脑的相对生物利用度(529%)和高脑靶向效率(315%),这证实了ZT成功输送到大脑。Terpesomes可能是安全的,能够提高ZT生物利用度的成功系统,具有高的脑靶向效率。
Zolmitriptan (ZT) is a potent second generation triptan, commonly administered to alleviate migraine attacks. ZT suffers various limitations; massive hepatic first pass metabolism, P-gp efflux transporters susceptibility, and limited (≈40%) oral bioavailability. Transdermal route of administration could be explored to enhance its bioavailability. A 23.31 full factorial design was constructed to developed twenty-four ZT loaded
terpesomes via thin film hydration technique. The influence of drug: phosphatidylcholine ratio, terpene type, terpene concentration and sodium deoxycholate concentration on the characterization of the developed ZT-loaded terpesomes was assessed. Particle size (PS), zeta potential (ZP), ZT entrapment efficiency (EE%), drug loading (DL%) and drug released percentages after 6 h (Q6h) were the selected dependent variables. Further morphological, crystallinity, and in-vivo histopathological studies were conducted for the optimum
terpesomes (T6). 99mTc-ZT and 99mTc-ZT-T6 gel were radio-formulated for in-vivo biodistribution studies in mice following transdermal application of 99mTc-ZT-T6 gel, relative to 99mTc-ZT oral solution. T6
terpesomes [comprising ZT and phosphatidylcholine (1:15), cineole (1% w/v) and sodium deoxycholate (0.1% w/v)] were optimum with respect to spherical PS (290.2 nm), ZP (-48.9 mV), EE% (83%), DL% (3.9%) and Q6h (92.2%) with desirability value of 0.85. The safety of the developed T6
terpesomes was verified by the in-vivo histopathological studies. 99mTc-ZT-T6 gel showed maximum brain concentration (5 ± 0.1%ID/ g) with highest brain to blood ratio of 1.92 ± 0.1 at 4 h post transdermal application. Significant improvement of ZT brain relative bioavailability (529%) and high brain targeting efficiency (315%) were revealed with 99mTc-ZT-T6 gel, which confirmed successful ZT delivery to the brain.
Terpesomes could be safe, successful systems capable of improving ZT bioavailability with high brain targeting efficiency.