Vlasova Maria A, Rytkönen Jussi, Riikonen Joakim, Tarasova Olga S, Mönkäre Juha, Kovalainen Miia, Närvänen Ale, Salonen Jarno, Herzig Karl-Heinz, Lehto Vesa-Pekka, Järvinen Kristiina
Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland.
Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland.
Eur J Pharm Sci. 2014 Oct 15;63:96-102. doi: 10.1016/j.ejps.2014.06.011. Epub 2014 Jun 22.
Intravenously administered nanocarriers are widely studied to improve the delivery of various therapeutic agents. However, recent in vivo studies have demonstrated that intravenously administered nanocarriers that do not contain any drug may affect cardiovascular function. Here we provide an example where the drug and the nanocarrier both affect the same cardiovascular parameters following intravenous administration. The peptide ghrelin antagonist (GhA) increases arterial pressure, while thermally hydrocarbonized porous silicon nanoparticles (THCPSi) transiently decrease it, as assessed with radiotelemetry in conscious rats. As a result, intravenous administration of GhA-loaded THCPSi nanoparticles partially antagonized GhA activity: arterial pressure was not increased. When the cardiovascular effects of GhA were blocked with atenolol pretreatment, GhA-loaded nanoparticles reduced arterial pressure to similar extent as drug-free nanoparticles. These data indicate that the biological activity of a drug delivered within a nanocarrier may be obscured by the biological responses induced by the nanocarrier itself.
静脉注射纳米载体被广泛研究以改善各种治疗剂的递送。然而，最近的体内研究表明，静脉注射不含任何药物的纳米载体可能会影响心血管功能。在此，我们提供一个例子，即静脉注射后，药物和纳米载体都会影响相同的心血管参数。肽胃饥饿素拮抗剂（GhA）会升高动脉血压，而热碳化多孔硅纳米颗粒（THCPSi）会使其短暂降低，这是通过对清醒大鼠进行无线电遥测评估得出的结果。因此，静脉注射载有GhA的THCPSi纳米颗粒会部分拮抗GhA的活性：动脉血压没有升高。当用阿替洛尔预处理阻断GhA的心血管效应时，载有GhA的纳米颗粒降低动脉血压的程度与不含药物的纳米颗粒相似。这些数据表明，纳米载体内递送的药物的生物活性可能会被纳米载体本身诱导的生物反应所掩盖。
