Brain-targeted delivery of losartan through functionalized liposomal nanoparticles for management of neurogenic hypertension.
Brain-targeted delivery of losartan through functionalized liposomal nanoparticles for management of neurogenic hypertension.
复制标题
通过功能化脂质体纳米颗粒脑靶向递送氯沙坦用于治疗神经源性高血压。
DOI：
10.1016/j.ijpharm.2023.122841
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发表时间：
2023
影响因子：
5.8
通讯作者：
Singh,Jagdish
中科院分区：
文献类型：
--
作者：
Lamptey,RichardNiiLante;Sun,Chengwen;Singh,Jagdish
越来越多的实验证据表明，阻断血管紧张素受体1型的活性可以防止自发性高血压大鼠高血压的发生。研究已经证明了这种策略通过回避手段，如脑血管内注射，使临床翻译困难。本研究旨在开发穿透素和转铁蛋白功能化脂质体作为安全递送氯沙坦钾（血管紧张素受体阻断剂）至脑的递送工具。通过后插入技术制备透皮素和转铁蛋白功能化的洛沙坦脂质体。氯沙坦脂质体为阳离子脂质体，粒径约150 nm，包封率为66.8 ± 1.5%。所有制剂均耐受良好，并在4 h内被原代细胞和培养细胞内化。此外，在Wistar京都大鼠体内评价了氯沙坦钾穿过血脑屏障的能力，无论是在溶液中还是在脂质体纳米颗粒中。静脉给药后，我们在接受游离氯沙坦溶液的大鼠脑组织中未发现可检测量的氯沙坦。结果表明，脂质体制剂可将氯沙坦递送至脑内，其脑内AUC和平均滞留时间分别为163.304 ± 13.09和8.623 ± 0.66 h。此外，在接受装载洛沙坦的脂质体的动物中未观察到毒性。
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 evaluatedin vivoin 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.