Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, United States.
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, United States.
Int J Pharm. 2023 Apr 25;637:122841. doi: 10.1016/j.ijpharm.2023.122841. Epub 2023 Mar 14.
There is mounting experimental evidence that blocking angiotensin receptor type 1 activity can prevent the occurrence of hypertension in spontaneously hypertensive rats. Studies have proved this strategy via evasive means, such as intracerebrovascular injections, making clinical translation difficult. This study aimed to develop penetratin and transferrin functionalized liposomes as a delivery tool to safely deliver losartan potassium (an angiotensin receptor blocker) to the brain. Penetratin and transferrin functionalized losartan-loaded liposomes were prepared via the post-insertion technique. Losartan-loaded liposomes were cationic, approximately 150 nm in size, entrapping 66.8 ± 1.5% of losartan. All formulations were well tolerated and internalized by primary and cultured cells in 4 h. Further, the ability to deliver losartan potassium across the blood-brain barrier was evaluated in vivo in Wistar Kyoto rats either in solution or when encapsulated within liposomal nanoparticles. Upon intravenous administration, we did not find a detectable amount of losartan in the brain tissue of rats that received free losartan solution. Contrarily, liposome formulations could deliver losartan to the brain, with a brain AUC and mean resident time of 163.304 ± 13.09 and 8.623 h ± 0.66, respectively. In addition, no toxicity was observed in the animals that received the losartan-loaded liposomes.
越来越多的实验证据表明，阻断血管紧张素受体 1 型活性可以预防自发性高血压大鼠高血压的发生。研究通过脑内注射等回避手段证明了这一策略，使得临床转化困难。本研究旨在开发穿透肽和转铁蛋白功能化脂质体作为一种输送工具，将氯沙坦钾（血管紧张素受体阻滞剂）安全地递送到大脑。通过后插入技术制备穿透肽和转铁蛋白功能化的氯沙坦钾载脂蛋白体。氯沙坦钾载脂蛋白体带正电荷，大小约为 150nm，包封氯沙坦钾 66.8±1.5%。所有配方均耐受良好，在 4 小时内被原代和培养细胞内化。此外，还在 Wistar Kyoto 大鼠体内评估了氯沙坦钾在溶液或包裹在脂质体纳米颗粒中的透过血脑屏障的能力。静脉注射后，我们在接受游离氯沙坦钾溶液的大鼠脑组织中未发现可检测量的氯沙坦钾。相反，脂质体配方可以将氯沙坦钾递送到大脑，其脑 AUC 和平均驻留时间分别为 163.304±13.09 和 8.623 h±0.66。此外，接受氯沙坦钾载脂蛋白体的动物没有观察到毒性。
